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Profile Name PIK3CA K567R
Gene Variant Detail

PIK3CA K567R (unknown)

Relevant Treatment Approaches

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
PIK3CA K944N colorectal cancer resistant Cetuximab + Fluorouracil Case Reports/Case Series Actionable In a clinical study, PIK3CA K944N was identified as a potential mechanism for acquired Erbitux (cetuximab) resistance in two colorectal cancer patients, which is supported by cell culture studies demonstrating resistance to Erbitux (cetuximab) and Fluorouracil combination treatment in colorectal cancer cells over expressing PIK3CA K944N (PMID: 28424201). 28424201
PIK3CA E542K PIK3CA F744L head and neck squamous cell carcinoma sensitive Sulindac Preclinical - Pdx Actionable In a preclinical study, Clinoril (sulindac) treatment reduced tumor growth rate in patient-derived xenograft (PDX) models of head and neck squamous cell carcinoma harboring PIK3CA mutations, including a model harboring PIK3CA E542K and PIK3CA F744L (PMID: 30683736). 30683736
PIK3CA V955I colorectal cancer resistant Cetuximab + Fluorouracil Case Reports/Case Series Actionable In a clinical study, PIK3CA V955I was identified as a potential mechanism for acquired Erbitux (cetuximab) resistance in a colorectal cancer patient, which is supported by cell culture studies demonstrating resistance to Erbitux (cetuximab) and Fluorouracil combination treatment in colorectal cancer cells over expressing PIK3CA V955I (PMID: 28424201). 28424201
PIK3CA K111N breast cancer sensitive BAY1125976 Preclinical - Cell culture Actionable In a preclinical study, BAY1125976 inhibited proliferation of a breast cancer cell line harboring PIK3CA K111N in culture (PMID: 27699769). 27699769
PIK3CA K111N estrogen-receptor positive breast cancer sensitive AZD8835 Preclinical Actionable In a preclinical study, AZD8835 inhibited proliferation of estrogen receptor (ER)-positive breast cancer cells harboring PIK3CA K111N in culture and induced tumor regression in xenograft models (PMID: 26839307). 26839307
PIK3CA K111N breast cancer sensitive Borussertib Preclinical - Cell culture Actionable In a preclinical study, borussertib inhibited proliferation of a breast cancer cell line harboring PIK3CA K111N in culture (PMID: 30858154). 30858154
PIK3CA K111N breast cancer sensitive ARQ 751 Preclinical - Cell culture Actionable In a preclinical study, a breast cancer cell line harboring PIK3CA K111N was sensitive to ARQ 751 in culture, demonstrating inhibition of cell growth (PMID: 26469692). 26469692
PIK3CA K111N breast cancer sensitive DHM25 Preclinical - Cell culture Actionable In a preclinical study, DHM25 increased cell death in a breast cancer cell line harboring PIK3CA K111N in culture (PMID: 26237138). 26237138
PIK3CA K111N breast cancer sensitive Miransertib Preclinical - Cell culture Actionable In a preclinical study, hormone receptor positive breast cancer cells harboring PIK3CA K111N were sensitive to Miransertib (ARQ092) in culture, demonstrating inhibition of cell growth (PMID: 26469692). 26469692
ERBB2 amp PIK3CA K111N breast cancer sensitive CH5132799 Preclinical - Cell line xenograft Actionable In a preclinical study, CH5132799 inhibited cell growth and Akt phosphorylation, and promoted apoptosis in a human breast cancer cell line harboring PIK3CA K111N and ERBB2 (HER2) amplification, and inhibited tumor growth in xenograft models (PMID: 21558396). 21558396
ERBB2 amp PIK3CA K111N breast cancer predicted - sensitive CYH33 Preclinical - Cell culture Actionable In a preclinical study, CYH33 inhibited proliferation of a breast cancer cell line harboring PIK3CA K111N and ERBB2 (HER2) amplification in culture (PMID: 30003928). 30003928
ERBB2 pos PIK3CA K111N Her2-receptor positive breast cancer sensitive Ado-trastuzumab emtansine Preclinical - Cell line xenograft Actionable In a preclinical study, Kadcyla (trastuzumab emtansine) inhibited survival of ERBB2 (HER2) positive breast cancer cells harboring PIK3CA K111N in culture, and induced tumor regression in cell line xenograft models (PMID: 26920887). 26920887
PIK3CA G1049R breast cancer sensitive Neratinib Preclinical Actionable In a preclinical study, Nerlynx (neratinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA G1049R in culture (PMID: 26627007). 26627007
PIK3CA G1049R Advanced Solid Tumor sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited survival of transformed cell lines overexpressing PIK3CA G1049R in culture (PMID: 26627007). 26627007
PIK3CA G1049R breast cancer resistant Buparlisib Preclinical - Cell culture Actionable In a preclinical study, breast cancer cells expressing PIK3CA G1049R demonstrated resistance to treatment with Buparlisib (BKM120) in culture (PMID: 29636477). 29636477
PIK3CA G1049R breast cancer sensitive Lapatinib Preclinical Actionable In a preclinical study, Tykerb (lapatinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA G1049R in culture (PMID: 26627007). 26627007
PIK3CA G1049R breast cancer sensitive MK2206 Preclinical Actionable In a preclinical study, MK2206 inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA G1049R in culture (PMID: 26627007). 26627007
PIK3CA G1049R breast cancer sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA G1049R in culture (PMID: 26627007). 26627007
PIK3CA G1049R breast cancer sensitive Dactolisib Preclinical Actionable In a preclinical study, BEZ235 inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA G1049R in culture (PMID: 26627007). 26627007
PIK3CA G1049R breast cancer sensitive Alpelisib Preclinical Actionable In a preclinical study, Alpelisib (BYL719) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA G1049R in culture (PMID: 26627007). 26627007
PIK3CA G1049R lung squamous cell carcinoma no benefit Taselisib Case Reports/Case Series Actionable In a Phase I (SWOG S1400B) trial, Taselisib (GDC-0032) treatment did not meet primary endpoint in patients with lung squamous cell carcinoma harboring PIK3CA mutations, a patients harboring PIK3CA G1047R did not demonstrated response (PMID: 31158500; NCT02785913). 31158500
PIK3CA F977Y head and neck squamous cell carcinoma resistant Pictilisib Preclinical - Cell culture Actionable In a preclinical study, a head and neck squamous cell carcinoma cell line harboring PIK3CA F977Y demonstrated resistance to growth inhibition by Pictilisib (GDC-0941) in culture (PMID: 30108165). 30108165
PIK3CA Q546X endometrial adenocarcinoma no benefit Copanlisib Case Reports/Case Series Actionable In a Phase II (NRG-GY008) trial, Aliqopa (copanlisib) was well tolerated but demonstrated limited efficacy, resulted in 1 stable disease and 1 progressive disease in 2 patients with endometrioid adenocarcinoma harboring PIK3CA Q546 mutations, and stable disease in a patient with serous endometrial adenocarcinoma harboring a PIK3CA Q546 mutation (PMID: 31934607). 31934607
PIK3CA E453Q PIK3CA H1047R breast cancer sensitive Everolimus Preclinical - Cell culture Actionable In a preclinical study, breast epithelial cells expressing PIK3CA E453Q and PIK3CA H1047R in cis demonstrated increased sensitivity to growth inhibition by Afinitor (everolimus) treatment compared to cells expressing individual PIK3CA mutations in culture (PMID: 31699932). 31699932
PIK3CA E453Q PIK3CA H1047R breast cancer sensitive Alpelisib Preclinical - Cell culture Actionable In a preclinical study, breast epithelial cells expressing PIK3CA E543Q and PIK3CA H1047R in cis demonstrated increased sensitivity to growth inhibition by Piqray (Alpelisib) treatment compared to cells expressing individual PIK3CA mutations in culture (PMID: 31699932). 31699932
PIK3CA E453Q PIK3CA H1047R breast cancer sensitive GDC-0077 Preclinical - Cell culture Actionable In a preclinical study, breast epithelial cells expressing PIK3CA E453Q and PIK3CA H1047R in cis demonstrated increased sensitivity to growth inhibition by GDC-0077 treatment compared to cells expressing individual PIK3CA mutations in culture (PMID: 31699932). 31699932
PIK3CA wild-type Advanced Solid Tumor sensitive PX-866 Phase I Actionable In a Phase I study, PX-866 demonstrated efficacy and was well tolerated in patients with advanced solid tumor with both PIK3CA wild-type and mutant status (PMID: 22693357). 22693357
PIK3CA wild-type Her2-receptor positive breast cancer sensitive Lapatinib + Paclitaxel + Trastuzumab Phase II Actionable In a Phase II trial, the combination of Taxol (paclitaxel) plus Herceptin (trastuzumab) and Tykerb (lapatinib) resulted in a higher pathologic complete remission rate in ERBB2 (HER2)-receptor positive breast cancer patients with PIK3CA wild-type compared to those harboring a PIK3CA mutation (PMID: 26245675). 26245675
PIK3CA wild-type triple-receptor negative breast cancer no benefit Palbociclib + Pictilisib Preclinical Actionable In a preclinical study, the combination of Ibrance (palbociclib) and Pictilisib (GDC-0941) did not improve growth inhibition compared to single drug treatment in PIK3CA wild-type, triple-receptor negative breast cancer cell lines in culture (PMID: 27020857). 27020857
PIK3CA wild-type colon cancer sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) treatment inhibited colony formation, and induced cell death and apoptosis in PIK3CA wild-type colon cancer cells in culture (PMID: 30944457). 30944457
PIK3CA wild-type colon cancer sensitive Selumetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Koselugo (selumetinib) treatment inhibited colony formation, and induced cell death and apoptosis in PIK3CA wild-type colon cancer cells in culture, and reduced tumor growth in a cell line xenograft model (PMID: 30944457). 30944457
PIK3CA wild-type Her2-receptor negative breast cancer no benefit Alpelisib Phase I Actionable In a Phase I trial, Alpelisib (BYL719) treatment resulted in no clinical benefit in 4 patients with ER-positive, ERBB2 (HER2)-negative breast cancer harboring PIK3CA mutations (PMID: 29401002; NCT01219699). 29401002
PIK3CA wild-type breast cancer no benefit Dactolisib + WEHI-539 Preclinical - Cell culture Actionable In a preclinical study, inhibition of Pi3k signaling by BEZ235 did not sensitize PIK3CA wild-type breast cancer cell lines to WEHI-539 in culture (PMID: 27974663). 27974663
PIK3CA wild-type breast cancer predicted - sensitive A-1210477 + WEHI-539 Preclinical - Cell culture Actionable In a preclinical study, combination of WEHI-539 and A-1210477 resulted in enhanced apoptosis in PIK3CA wild-type breast cancer cell lines in culture (PMID: 27974663). 27974663
PIK3CA wild-type colon cancer sensitive Pimasertib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) treatment inhibited colony formation, and induced cell death and apoptosis in PIK3CA wild-type colon cancer cells in culture (PMID: 30944457). 30944457
PIK3CA wild-type colon cancer sensitive Refametinib Preclinical - Cell culture Actionable In a preclinical study, Refametinib (BAY86-9766) treatment inhibited colony formation, and induced cell death and apoptosis in PIK3CA wild-type colon cancer cells in culture (PMID: 30944457). 30944457
BRAF V600E/K PIK3CA wild-type melanoma no benefit A66 Preclinical Actionable In a preclinical study, A66 did not inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). 26137449
BRAF V600E/K PIK3CA wild-type melanoma sensitive Vemurafenib + ZSTK474 Preclinical Actionable In a preclinical study, ZSTK474 and Zelboraf (vemurafenib) worked synergistically to inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). 26137449
BRAF V600E/K PIK3CA wild-type melanoma no benefit Idelalisib Preclinical Actionable In a preclinical study, Zydelig (idelalisib) did not inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). 26137449
BRAF V600E/K PIK3CA wild-type melanoma sensitive Selumetinib + ZSTK474 Preclinical - Cell line xenograft Actionable In a preclinical study, Selumetinib (AZD6244) and ZSTK474 combination treatment inhibited proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture, and synergistically inhibited tumor growth in cell line xenograft models (PMID: 26137449). 26137449
BRAF V600E/K PIK3CA wild-type melanoma sensitive Dactolisib + Selumetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Koselugo (selumetinib) and BEZ235 combination treatment inhibited proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture, and synergitically inhibited tumor growth in cell line xenograft models (PMID: 26137449). 26137449
BRAF V600E/K PIK3CA wild-type melanoma sensitive Dactolisib + Vemurafenib Preclinical Actionable In a preclinical study, BEZ235 and Zelboraf (vemurafenib) worked synergistically to inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). 26137449
BRAF V600E/K PIK3CA wild-type melanoma sensitive Selumetinib + Vemurafenib Preclinical Actionable In a preclinical study, Selumetinib (AZD6244) and Zelboraf (vemurafenib) worked synergistically to inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). 26137449
BRAF V600E/K PIK3CA wild-type melanoma no benefit TGX-221 Preclinical Actionable In a preclinical study, TGX-221 did not inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). 26137449
ERBB2 amp PIK3CA wild-type uterine corpus serous adenocarcinoma sensitive Neratinib Preclinical - Cell line xenograft Actionable In a preclinical study, Nerlynx (neratinib) delayed cell cycle activity during treatment of a uterine serous carcinoma cell line harboring PIK3CA wild-type and ERBB2 (HER2) amplification in culture, and inhibited tumor growth in xenograft models (PMID: 26333383). 26333383
ERBB2 amp PIK3CA wild-type Her2-receptor positive breast cancer predicted - sensitive Poziotinib Phase II Actionable In a Phase II trial, the presence of high ERBB2 (HER2) copy number and wild-type PIK3CA correlated with improved progression-free survival (HR=0.45, p=0.024) in patients with metastatic Erbb2 (Her2)-positive (amplification or overexpression) breast cancer treated with Poziotinib (HM781-36B) (PMID: 30720867, NCT02418689). 30720867
ERBB2 amp PIK3CA wild-type uterine corpus serous adenocarcinoma sensitive Neratinib + Taselisib Preclinical - Cell culture Actionable In a preclinical study, the combination of Taselisib (GDC-0032) and Nerlynx (neratinib) delayed cell cycle activity in a uterine serous carcinoma cell line harboring PIK3CA wild-type and ERBB2 (HER2) amplification in culture (PMID: 26333383). 26333383
ERBB2 amp PIK3CA wild-type uterine corpus serous adenocarcinoma sensitive Taselisib Preclinical - Cell line xenograft Actionable In a preclinical study, Taselisib (GDC-0032) did not result in delay of cell cycle activity during treatment of a uterine serous carcinoma cell line harboring PIK3CA wild-type and ERBB2 (HER2) amplification in culture, however, did result in tumor growth inhibition in xenograft models (PMID: 26333383). 26333383
NRAS mut PIK3CA wild-type colorectal cancer predicted - sensitive TAK-733 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cell lines harboring mutations in KRAS or NRAS and with wild-type PIK3CA demonstrated a trend toward increased sensitivity to TAK-733 in culture (PMID: 26439693). 26439693
BRAF mut PIK3CA wild-type colorectal cancer predicted - sensitive TAK-733 Preclinical - Pdx & cell culture Actionable In a preclinical study, mutations in BRAF, KRAS, or NRAS were associated with sensitivity to TAK-733 in colorectal cancer cell lines in culture, and patient-derived xenograft models harboring KRAS or BRAF mutations with wild-type PIK3CA demonstrated a trend toward higher tumor growth inhibition following TAK-733 treatment (PMID: 26439693). 26439693
CTNNB1 over exp PIK3CA wild-type colon cancer resistant Refametinib Preclinical - Cell culture Actionable In a preclinical study, overexpression of CTNNB1 in PIK3CA wild-type colon cancer cells suppressed cell death following Refametinib (BAY86-9766) treatment in culture (PMID: 30944457). 30944457
CTNNB1 over exp PIK3CA wild-type colon cancer resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, overexpression of CTNNB1 in PIK3CA wild-type colon cancer cells suppressed cell death following Mekinist (trametinib) treatment in culture (PMID: 30944457). 30944457
CTNNB1 over exp PIK3CA wild-type colon cancer resistant Pimasertib Preclinical - Cell culture Actionable In a preclinical study, overexpression of CTNNB1 in PIK3CA wild-type colon cancer cells suppressed cell death following Pimasertib (MSC1936369B) treatment in culture (PMID: 30944457). 30944457
CTNNB1 over exp PIK3CA wild-type colon cancer resistant Selumetinib Preclinical - Cell culture Actionable In a preclinical study, overexpression of CTNNB1 in PIK3CA wild-type colon cancer cells suppressed cell death following Koselugo (selumetinib) treatment in culture (PMID: 30944457). 30944457
ERBB2 amp PIK3CA E545K PIK3CA K567R Her2-receptor positive breast cancer sensitive Gedatolisib Preclinical - Cell line xenograft Actionable In a preclinical study, Gedatolisib (PKI-587) inhibited PI3K signaling, cell growth and induced apoptosis in human breast cancer cells harboring ERBB2 (HER2) amplification, PIK3CA E545K, and PIK3CA K567R in culture and in cell line xenografts (PMID: 21325073, PMID: 17314276). 17314276 21325073
PIK3CA exon10 Her2-receptor negative breast cancer predicted - sensitive Everolimus Phase III Actionable In a retrospective analysis of a Phase III trial (BOLERO-2), Afinitor (everolimus) demonstrated greater benefit on progression-free survival in patients with hormone receptor-positive, Erbb2 (Her2)-negative breast cancer harboring PIK3CA exon 10 (reported as exon 9) mutations (HR=0.26) compared to patients harboring PIK3CA exon 21 (reported as exon 20) mutations (HR=0.56) (PMID: 26503204; NCT00863655). 26503204
PIK3CA F930S colorectal cancer resistant Cetuximab + Fluorouracil Case Reports/Case Series Actionable In a clinical study, PIK3CA F930S was identified as a potential mechanism for acquired Erbitux (cetuximab) resistance in a colorectal cancer patient, which is consistent with cell culture studies demonstrating moderate resistance to Erbitux (cetuximab) and Fluorouracil combination treatment in colorectal cancer cells over expressing PIK3CA F930S (PMID: 28424201). 28424201
PIK3CA H1047Y endometrial cancer sensitive CH5132799 Preclinical - Cell line xenograft Actionable In a preclinical study, CH5132799 inhibited cell growth in a human endometrial cancer cell line harboring a PIK3CA H1047Y mutation, and inhibited tumor growth in xenograft models (PMID: 21558396). 21558396
PIK3CA H1047Y glioblastoma multiforme sensitive YM-024 Preclinical Actionable In a preclinical study, glioblastoma cell lines harboring PIK3CA H1047Y demonstrated increased sensitivity to YM-204 induced growth inhibition (PMID: 24718026). 24718026
PIK3CA D549Y urinary bladder cancer decreased response Pictilisib Preclinical - Pdx Actionable In a preclinical study, Pictilisib (GDC-0941) demonstrated limited tumor growth inhibition and survival benefit in patient-derived xenograft (PDX) models of bladder cancer harboring PIK3CA D549Y (PMID: 28808038). 28808038
PIK3CA E542K breast cancer resistant Buparlisib Preclinical - Cell culture Actionable In a preclinical study, breast cancer cells expressing PIK3CA E542K demonstrated resistance to treatment with Buparlisib (BKM120) in culture (PMID: 29636477). 29636477
PIK3CA E542K Her2-receptor negative breast cancer no benefit Everolimus Phase III Actionable In a retrospective analysis of a Phase III trial (BOLERO-2), Afinitor (everolimus) demonstrated comparable progression-free survival benefit in patients with hormone receptor-positive, Erbb2 (Her2)-negative breast cancer harboring wild-type (HR=0.43) or mutant (HR=0.37) PIK3CA, similar benefit was observed in subgroups harboring PIK3CA H1047R (HR=0.37) and PIK3CA E545K/E542K (HR=0.30) (PMID: 28183140; NCT00863655). 28183140
PIK3CA E542K thyroid gland papillary carcinoma sensitive MK2206 Preclinical - Cell culture Actionable In a preclinical study, MK2206 inhibited AKT activation, proliferation, and growth of thyroid cancer cell lines with PI3K/AKT pathway alterations in culture, including a papillary thyroid cancer cell line harboring PIK3CA E542K (PMID: 21289267). 21289267
PIK3CA E542K colorectal cancer resistant Cetuximab + Fluorouracil Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells over expressing PIK3CA E542K were resistant to Erbitux (cetuximab) and Fluorouracil combination treatment in culture (PMID: 28424201). 28424201
PIK3CA E542K endometrial adenocarcinoma no benefit Copanlisib Case Reports/Case Series Actionable In a Phase II (NRG-GY008) trial, Aliqopa (copanlisib) was well tolerated but demonstrated limited efficacy, resulted in stable disease in 2 patients with serous endometrial adenocarcinoma harboring PIK3CA E542K (PMID: 31934607). 31934607
PIK3CA E542K colon adenocarcinoma sensitive VS-5584 Preclinical Actionable In preclinical studies, VS-5584 demonstrated efficacy in a variety of cancer cell lines, particularly those harboring PIK3CA mutations (PMID: 23270925). 23270925
PIK3CA E542K gastrointestinal system cancer sensitive Capivasertib Preclinical Actionable In a preclinical study, gastric cancer cells harboring PI3KCA E542K mutations were sensitive to the AKT inhibitor AZD5363 (PMID: 24088382). 24088382
PIK3CA E542K breast cancer sensitive Neratinib Preclinical Actionable In a preclinical study, Nerlynx (neratinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA E542K in culture (PMID: 26627007). 26627007
PIK3CA E542K Advanced Solid Tumor sensitive Sirolimus Preclinical Actionable In a preclinical study, Rapamune (sirolimus) demonstrated efficacy in inhibiting transformation of cultured cells containing PIK3CA E542K mutations (PMID: 15647370). 15647370
PIK3CA E542K breast cancer sensitive Alpelisib Preclinical - Cell culture Actionable In a preclinical study, Alpelisib (BYL719) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA E542K in culture (PMID: 26627007). 26627007
PIK3CA E542K thyroid gland papillary carcinoma sensitive MK2206 + Temsirolimus Preclinical - Cell culture Actionable In a preclinical study, MK2206 suppressed activation of AKT induced by Torisel (temsirolimus), and MK2206 and Torisel (temsirolimus) demonstrated synergy in inhibiting growth of a papillary thyroid cancer cell line harboring PIK3CA E542K in culture (PMID: 21289267). 21289267
PIK3CA E542K stomach cancer sensitive Capivasertib Case Reports/Case Series Actionable In a clinical case study, treatment with Capivasertib (AZD5363) in a patient with gastric cancer harboring PIK3CA E542K resulted in a partial response, and in preclinical studies, led to decreased cell proliferation in a gastric cancer cell line harboring PIK3CA E542K (PMID: 32070411). 32070411
PIK3CA E542K breast cancer sensitive Lapatinib Preclinical Actionable In a preclinical study, Tykerb (lapatinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA E542K in culture (PMID: 26627007). 26627007
PIK3CA E542K colorectal cancer predicted - sensitive Cetuximab + Irinotecan Case Reports/Case Series Actionable In a retrospective analysis, treatment with the combination of Erbitux (cetuximab) and Camptosar (irinotecan) resulted in a partial response in 50% (1/2) and stable disease in 50% (1/2) of colorectal carcinoma patients harboring a PIK3CA E542K mutation (PMID: 25714871). 25714871
PIK3CA E542K cervical squamous cell carcinoma sensitive Gemcitabine + LY2780301 Phase Ib/II Actionable In a Phase Ib trial, a patient with cervical squamous cell carcinoma harboring PIK3CA E542K demonstrated a partial response when treated with a combination of LY2780301 and Gemzar (gemcitabine) (PMID: 28750271). 28750271
PIK3CA E542K head and neck squamous cell carcinoma sensitive GDC-0980 Phase I Actionable In a Phase I trial, Apitolisib (GDC-0980) treatment resulted in a partial response in a patient with head and neck squamous cell carcinoma harboring a PIK3CA E542K mutation (PMID: 26787751). 26787751
PIK3CA E542K malignant glioma sensitive Buparlisib + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Buparlisib (BKM120) and Koselugo (selumetinib) led to a synergistic effect, resulting in greater growth inhibition of astrocytoma cells expressing PIK3CA E542K than cells with wild-type PIK3CA in culture (PMID: 29975751). 29975751
PIK3CA E542K breast cancer sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA E542K in culture (PMID: 26627007). 26627007
PIK3CA E542K colorectal cancer sensitive PD-0325901 + Pictilisib Preclinical - Cell line xenograft Actionable In preclinical studies, the combination of GDC-0941 and PD-0325901 (PI3K and MEK inhibitors, respectively) inhibited tumor growth in colorectal cancer cell line xenograft models (PMID: 24339963). 24339963
PIK3CA E542K breast cancer sensitive CH5132799 Preclinical Actionable In a preclinical study, CH5132799 inhibited proliferation of a breast cancer cell line harboring PIK3CA E542K in culture (PMID: 21558396). 21558396
PIK3CA E542K breast cancer sensitive MK2206 Preclinical Actionable In a preclinical study, MK2206 inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA E542K in culture (PMID: 26627007). 26627007
PIK3CA E542K breast cancer sensitive Dactolisib Preclinical Actionable In a preclinical study, BEZ235 inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA E542K in culture (PMID: 26627007). 26627007
PIK3CA E542K head and neck squamous cell carcinoma predicted - sensitive Alpelisib + Cetuximab + Radiotherapy Case Reports/Case Series Actionable In a Phase Ib trial, 11 of 11 patients with metastatic head and neck squamous cell carcinoma demonstrated no evidence of disease at 3 to 4 months following treatment with Piqray (alpelisb) in combination with Erbitux (cetuximab) and intensity modulated radiation therapy (IMRT), and PIK3CA E545K was identified in one patient with oropharyngeal squamous cell carcinoma who had a near complete radiologic response within 8 days of starting IMRT (PMID: 31678634). 31678634
PIK3CA E542K lung squamous cell carcinoma no benefit Taselisib Case Reports/Case Series Actionable In a Phase I (SWOG S1400B) trial, Taselisib (GDC-0032) treatment did not meet primary endpoint in patients with lung squamous cell carcinoma harboring PIK3CA mutations, none of the 6 patients harboring PIK3CA E542K demonstrated response (PMID: 31158500; NCT02785913). 31158500
PIK3CA E542K breast cancer sensitive Miransertib Preclinical - Cell culture Actionable In a preclinical study, a hormone breast cancer cell line harboring PIK3CA E542K was sensitive to Miransertib (ARQ092) in culture, demonstrating inhibition of cell growth (PMID: 26469692). 26469692
PIK3CA E542K PIK3CA amp lung squamous cell carcinoma sensitive Alpelisib Preclinical - Pdx Actionable In a preclinical study, Alpelisib (BYL719) treatment resulted in response in a lung squamous cell carcinoma patient-derived xenograft (PDX) model harboring PIK3CA E542K and PIK3CA amplification (PMID: 30093452). 30093452
PIK3CA E542K PIK3CA amp lung squamous cell carcinoma sensitive Buparlisib Preclinical - Pdx Actionable In a preclinical study, Buparlisib (BKM120) treatment resulted in inhibition of AKT and S6 phosphorylation and durable response in a lung squamous cell carcinoma patient-derived xenograft (PDX) model harboring PIK3CA E542K and PIK3CA amplification (PMID: 30093452). 30093452
CDKN2A loss PIK3CA E542K PIK3CA amp lung squamous cell carcinoma sensitive Buparlisib + Palbociclib Preclinical - Pdx Actionable In a preclinical study, treatment with the combination of Buparlisib (BYL719) and Ibrance (palbociclib) resulted in increased tumor growth inhibition compared to either agent alone in a patient-derived xenograft (PDX) model of lung squamous cell carcinoma harboring PIK3CA E542K and PIK3CA amplification, with p16 (CDKN2A) loss (PMID: 30093452). 30093452
ERBB2 pos PIK3CA E542K Her2-receptor positive breast cancer predicted - sensitive Neratinib Phase III Actionable In a Phase III trial (ExteNET), Nerlynx (neratinib) treatment resulted in improved 5-year invasive disease-free survival (92.4% vs 84.5%, HR=0.41, p=0.028) and clinical benefit (HR=0.40, p=0.041) compared to placebo in patients with ERBB2 (HER2)-positive early breast cancer who completed trastuzumab-based adjuvant therapy, and harbored PIK3CA amplification (n=61) or mutations (n=210), including H1047R (n=110), E542K (n=18), and E545K/D (n=82) (PMID: 30867034; NCT00878709). 30867034
HRAS mut PIK3CA E542K malignant glioma sensitive Buparlisib + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Buparlisib (BKM120) and Koselugo (selumetinib) led to a synergistic effect, resulting in growth inhibition of astrocytoma cells with an HRAS mutation expressing PIK3CA E542K in culture, but at a higher drug concentration compared to cells without mutant HRAS (PMID: 29975751). 29975751
BRAF V600E PIK3CA H1047K melanoma sensitive Miransertib + Trametinib Preclinical - Pdx Actionable In a preclinical study, a melanoma patient-derived xenograft (PDX) model harboring BRAF V600E and PIK3CA H1047K was sensitive to the combination treatment of Miransertib (ARQ092) and Mekinist (trametinib), demonstrating a greater inhibition of tumor growth when compared to either agent alone (PMID: 26469692). 26469692
ERBB2 amp PIK3CA E542X Her2-receptor positive breast cancer decreased response Poziotinib Phase II Actionable In a Phase II trial, the presence of PIK3CA activating mutations including E542X, E545X, and H1047X correlated with shorter progression-free survival (2.66 months) compared to PIK3CA wild-type or other mutations (4.24 month, HR=1.68, p=0.033) in patients with metastatic Erbb2 (Her2)-positive (amplification or overexpression) breast cancer treated with Poziotinib (HM781-36B) (PMID: 30720867, NCT02418689). 30720867
ERBB2 over exp PIK3CA E542X Her2-receptor positive breast cancer decreased response Poziotinib Phase II Actionable In a Phase II trial, the presence of PIK3CA activating mutations including E542X, E545X, and H1047X correlated with shorter progression-free survival (2.66 months) compared to PIK3CA wild-type or other mutations (4.24 month, HR=1.68, p=0.033) in patients with metastatic Erbb2 (Her2)-positive (amplification or overexpression) breast cancer treated with Poziotinib (HM781-36B) (PMID: 30720867, NCT02418689). 30720867
PIK3CA P539R breast cancer sensitive BAY1125976 Preclinical - Cell culture Actionable In a preclinical study, BAY1125976 inhibited proliferation of a breast cancer cell line harboring PIK3CA P539R in culture (PMID: 27699769). 27699769
PIK3CA P539R breast cancer predicted - sensitive CYH33 Preclinical - Cell culture Actionable In a preclinical study, CYH33 inhibited proliferation of a breast cancer cell line harboring PIK3CA P539R in culture (PMID: 30003928). 30003928
PIK3CA P539R PIK3CA H1047R breast cancer sensitive PF-04691502 Preclinical - Cell culture Actionable In a preclinical study, PF-04691502 inhibited Akt phosphorylation and proliferation of breast cancer cells harboring both PIK3CA P539R and H1047R in culture (PMID: 21750219). 21750219
PIK3CA P539R PIK3CA H1047R breast cancer sensitive Miransertib Preclinical - Cell culture Actionable In a preclinical study, breast cancer cells harboring PIK3CA P539R and H1047R were sensitive to Miransertib (ARQ092) in culture, demonstrating inhibition of cell growth (PMID: 26469692). 26469692
PIK3CA P539R PIK3CA H1047R breast cancer sensitive ARQ 751 Preclinical - Cell culture Actionable In a preclinical study, a breast cancer cell line harboring PIK3CA P539R and PH1047R was sensitive to ARQ 751 in culture, demonstrating inhibition of cell growth (PMID: 26469692). 26469692
ERBB2 pos PIK3CA E545D Her2-receptor positive breast cancer predicted - sensitive Neratinib Phase III Actionable In a Phase III trial (ExteNET), Nerlynx (neratinib) treatment resulted in improved 5-year invasive disease-free survival (92.4% vs 84.5%, HR=0.41, p=0.028) and clinical benefit (HR=0.40, p=0.041) compared to placebo in patients with ERBB2 (HER2)-positive early breast cancer who completed trastuzumab-based adjuvant therapy, and harbored PIK3CA amplification (n=61) or mutations (n=210), including H1047R (n=110), E542K (n=18), and E545K/D (n=82) (PMID: 30867034; NCT00878709). 30867034
PIK3CA act mut Advanced Solid Tumor sensitive Everolimus Preclinical - Cell line xenograft Actionable In a preclinical study, Afinitor (everolimus) demonstrated efficacy in multiple cancer cell lines in culture and xenograft models with PIK3CA activating mutations (PMID: 20664172). 20664172
PIK3CA act mut lung non-small cell carcinoma sensitive Pictilisib Preclinical - Cell line xenograft Actionable In preclinical studies, the PI3K inhibitor GDC-0941 demonstrated efficacy against NSCLC tumor cell lines in culture and in xenograft models harboring alterations in the PI3K pathway (PMID: 23136191). 23136191
PIK3CA act mut estrogen-receptor positive breast cancer predicted - sensitive Capivasertib + Tamoxifen Preclinical - Cell culture Actionable In a preclinical study, the combination of AZD5363 and 4-hydroxytamoxifen (4-OHT) worked synergistically or additively to inhibit growth of several estrogen receptor-positive breast cancer cell lines in culture, including cell lines with PIK3CA activating mutations, and overcame tamoxifen resistance in a resistant cell line (PMID: 26116361). 26116361
PIK3CA act mut Advanced Solid Tumor sensitive BAY1125976 Preclinical Actionable In a preclinical study, BAY1125976 demonstrated anti-tumor efficacy in multiple xenograft tumor models of different cancers with PIK3CA mutations or PTEN deletions and displayed synergy with other anti-cancer therapies (Cancer Res 2013;73(8 Suppl):Abstract nr 2050). detail...
PIK3CA act mut Advanced Solid Tumor sensitive GSK1059615 Preclinical Actionable In a preclinical study, solid tumor cell lines harboring PIK3CA activating mutations demonstrated increased sensitivity to GSK1059615 in culture (Clin Cancer Res October 1, 2008 14; B37). detail...
PIK3CA act mut breast cancer predicted - sensitive Dactolisib + WEHI-539 Preclinical - Cell culture Actionable In a preclinical study, inhibition of Pi3k signaling by BEZ235 sensitized breast cancer cell lines harboring PIK3CA activating mutations to WEHI-539 in culture (PMID: 27974663). 27974663
PIK3CA act mut breast cancer predicted - sensitive Vistusertib + WEHI-539 Preclinical - Cell culture Actionable In a preclinical study, the ATP-competitive mTORC1/2 inhibitor Vistusertib (AZD2014) sensitized breast cancer cell lines harboring PIK3CA activating mutations to WEHI-539 in culture (PMID: 27974663). 27974663
PIK3CA act mut Advanced Solid Tumor sensitive Metformin Preclinical Actionable In a preclinical study, Glucophage (metformin) demonstrated efficacy in treating dietary restriction-resistant human xenograft tumors harboring a PIK3CA-activating mutation (PMID: 23986086). 23986086
PIK3CA act mut Advanced Solid Tumor conflicting Taselisib Preclinical - Cell line xenograft Actionable In a preclinical study, Taselisib (GDC-0032) effectively suppressed growth of multiple tumor types in cell line xenograft models, with greater selectivity for PIK3CA activating mutants (PMID: 23662903). 23662903
PIK3CA act mut Advanced Solid Tumor conflicting Taselisib Phase II Actionable In a Phase II (MATCH) trial, Taselisib (GDC-0032) treatment resulted in no objective response (0/65) but prolonged stable disease (estimated 6-month progression-free survival rate 27%) in patients with advanced solid tumors harboring PIK3CA activating mutations (J Clin Oncol 36, 2018 (suppl; abstr 101); NCT02465060). detail...
PIK3CA act mut breast cancer no benefit Dactolisib + Venetoclax Preclinical - Cell culture Actionable In a preclinical study, inhibition of Pi3k signaling by BEZ235 did not sensitize breast cancer cell lines harboring PIK3CA activating mutations to Venclexta (venetoclax) in culture (PMID: 27974663). 27974663
PIK3CA act mut lung non-small cell carcinoma predicted - resistant Osimertinib Case Reports/Case Series Actionable In a retrospective analysis, activating PIK3CA mutations were identified in 6 of 100 patients with non-small cell lung cancer at treatment discontinuation of Tagrisso (osimertinib) (PMID: 31839416). 31839416
PIK3CA act mut lung small cell carcinoma predicted - sensitive Navitoclax + Pictilisib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Navitoclax (ABT-263) and GDC-0941 resulted in increased tumor growth delay and apoptosis in a small cell lung cancer cell line xenograft model harboring a PIK3CA activating mutation compared to either drug alone (PMID: 27197306). 27197306
PIK3CA act mut breast cancer no benefit Alpelisib + WEHI-539 Preclinical - Cell culture Actionable In a preclinical study, Alpelisib (BYL719) did not sensitize breast cancer cell lines harboring PIK3CA activating mutations to WEHI-539 in culture (PMID: 27974663). 27974663
PIK3CA act mut breast cancer predicted - sensitive Sapanisertib + WEHI-539 Preclinical - Cell culture Actionable In a preclinical study, the ATP-competitive mTORC1/2 inhibitor Sapanisertib (MLN0128) sensitized breast cancer cell lines harboring PIK3CA activating mutations to WEHI-539 in culture (PMID: 27974663). 27974663
PIK3CA act mut ovarian clear cell adenocarcinoma sensitive Dactolisib Preclinical Actionable In a preclinical study, BEZ235 demonstrated efficacy in mouse xenograft models of ovarian clear cell adenocarcinoma with PIK3CA mutations (PMID: 24927217). 24927217
PIK3CA act mut triple-receptor negative breast cancer predicted - sensitive Bevacizumab + Doxorubicin + Temsirolimus Phase I Actionable In a Phase I trial, triple-receptor negative breast cancer patients, including those with PIK3CA activating mutations, demonstrated an overall response rate of 21% (11/52) and clinical benefit rate of 40% (21/52) when treated with a combination of Avastin (bevacizumab), Adriamycin (doxorubicin), and either Afinitor (everolimus) or Torisel (temsirolimus) (PMID: 27893038). 27893038
PIK3CA act mut breast cancer predicted - sensitive MK2206 + Ridaforolimus Phase I Actionable In a Phase I clinical trial, Ridaforolimus in combination with MK-2206 demonstrated clinical activity in breast cancer patients expressing a PI3K pathway dependent gene expression signature, with complete response in 14.3% (2/14), partial response in 12.5% (2/16), and 2 patients achieving stable disease (PMID: 26187616). 26187616
PIK3CA act mut head and neck squamous cell carcinoma predicted - sensitive AZD8055 + Cetuximab Preclinical - Pdx Actionable In a preclinical study, two head and neck squamous cell carcinoma patient-derived xenograft (PDX) models harboring a PIK3CA activating mutation demonstrated greater delayed tumor growth when treated with a combination of AZD8055 and Erbitux (cetuximab) compared to either agent alone (PMID: 28446642). 28446642
PIK3CA act mut breast cancer no benefit Buparlisib + WEHI-539 Preclinical - Cell culture Actionable In a preclinical study, Buparlisib (BKM120) did not sensitize breast cancer cell lines harboring PIK3CA activating mutations to WEHI-539 in culture (PMID: 27974663). 27974663
PIK3CA act mut triple-receptor negative breast cancer predicted - sensitive Bevacizumab + Doxorubicin + Everolimus Phase I Actionable In a Phase I trial, triple-receptor negative breast cancer patients, including those with PIK3CA activating mutations, demonstrated an overall response rate of 21% (11/52) and clinical benefit rate of 40% (21/52) when treated with a combination of Avastin (bevacizumab), Adriamycin (doxorubicin), and either Afinitor (everolimus) or Torisel (temsirolimus) (PMID: 27893038). 27893038
PIK3CA act mut lung squamous cell carcinoma predicted - sensitive Alpelisib Preclinical - Pdx Actionable In a preclinical study, Alpelisib (BYL719) treatment resulted in responses in multiple lung squamous cell carcinoma patient-derived xenograft (PDX) models harboring PIK3CA E545K or E542K mutations, including models with PIK3CA amplification or PTEN loss (PMID: 30093452). 30093452
PIK3CA act mut triple-receptor negative breast cancer predicted - sensitive Capivasertib + Paclitaxel Phase II Actionable In a Phase II trial (PAKT), addition of Capivasertib (AZD5363) to Taxol (paclitaxel) as first-line therapy significantly improved median progression-free survival (9.3 vs 3.7 months, HR=0.30, p=0.01) and reduced risk (66%, HR=0.34, p=0.04) compared to Taxol (paclitaxel) alone in patients with metastatic triple-negative breast cancer harboring activating mutations in AKT1 (E17K, n=1) or PIK3CA (n=17), or inactivating mutations or gene loss in PTEN (n=13) (PMID: 31841354; NCT02423603). 31841354
PIK3CA act mut Advanced Solid Tumor sensitive Ipatasertib + Paclitaxel Phase Ib/II Actionable In a Phase Ib trial, Ipatasertib (GDC-0068) in combination with Abraxane (paclitaxel) demonstrated safety and anti-tumor activity in patients with advanced solid tumors, including patients with PIK3CA activating mutations (Annals of Oncology (2014) 25 (suppl_4): iv146-iv164. 10.1093/annonc/mdu331). detail...
PIK3CA act mut breast cancer sensitive MK2206 Preclinical Actionable In a preclinical study, breast cancer cell lines harboring activating mutations in PIK3CA had increased sensitivity to MK2206 in cell culture (PMID: 22932669). 22932669
PIK3CA act mut lung squamous cell carcinoma predicted - sensitive Buparlisib Preclinical - Pdx Actionable In a preclinical study, Buparlisib (BKM120) treatment resulted in inhibition of AKT and S6 phosphorylation and durable responses in 4/5 lung squamous cell carcinoma patient-derived xenograft (PDX) models harboring PIK3CA E545K or E542K mutations, 3 that also had PIK3CA amplification and 1 with PTEN loss (PMID: 30093452). 30093452
PIK3CA act mut Advanced Solid Tumor sensitive Afuresertib Preclinical Actionable In a preclinical study, various tumor cell lines harboring PI3KCA activating mutations demonstrated increased sensitivity to Afuresertib (GSK2110183) in cultured cells (PMID: 24978597). 24978597
PIK3CA act mut head and neck squamous cell carcinoma sensitive Gedatolisib Preclinical Actionable In a preclinical study, PF-05212384 decreased viability of head and neck squamous carcinoma cells harboring a PIK3CA activating mutation in cell culture (PMID: 24823695). 24823695
PIK3CA act mut breast cancer predicted - sensitive Torin 1 + WEHI-539 Preclinical - Cell culture Actionable In a preclinical study, the ATP-competitive mTORC1/2 inhibitor Torin1 sensitized breast cancer cell lines harboring PIK3CA activating mutations to WEHI-539 in culture (PMID: 27974663). 27974663
PIK3CA act mut breast cancer sensitive Copanlisib Phase I Actionable In a Phase I clinical trial, treatment with Aliqopa (copanlisib) resulted in partial response in one and stable disease in another patient with breast cancer harboring activating PIK3CA mutations (PMID: 27672108; NCT00962611). 27672108
PIK3CA act mut breast cancer sensitive Copanlisib Preclinical Actionable In a preclinical study, breast cancer cell lines with a PIK3CA activating mutation and/or ERBB2 (HER2) over expression demonstrated increased sensitivity to inhibition of proliferation by Aliqopa (copanlisib) in culture, compared to ERBB2 (HER2)-negative and wild-type PIK3CA cell lines (PMID: 24170767). 24170767
ERBB2 pos PIK3CA act mut Her2-receptor positive breast cancer predicted - sensitive Buparlisib + Trastuzumab Phase I Actionable In a Phase I trial, the combination of Buparlisib (BKM120) and Herceptin (trastuzumab) was well tolerated and resulted in some preliminary efficacy in patients with ERBB2 (HER2)-positive breast cancer harboring PIK3CA activating mutations and/or PTEN mutations that had progressed on trastuzumab-based therapy (PMID: 24470511). 24470511
ERBB2 pos PIK3CA act mut uterine cancer sensitive Taselisib Preclinical Actionable In a preclinical study, Taselisib (GDC-0032) inhibited growth of HER2 positive uterine cancer cell lines with PIK3CA mutations (PMID: 25172762). 25172762
ERBB2 pos PIK3CA act mut Her2-receptor positive breast cancer decreased response Trastuzumab Clinical Study - Cohort Actionable In a clinical study, ERBB2 (HER2)-positive breast cancer patients with PI3K pathway activation resulting from low PTEN expression and/or PIK3CA activating mutations demonstrated decreased progression-free survival following treatment with Herceptin (trastuzumab) compared to patients without PI3K pathway activation (PMID: 17936563). 17936563
ERBB2 pos PIK3CA act mut Her2-receptor positive breast cancer decreased response Trastuzumab Clinical Study - Cohort Actionable In a retrospective analysis, ERBB2 (HER2)-positive breast cancer patients with PI3K pathway activation due to PTEN loss and/or PIK3CA activating mutation demonstrated a decreased median progression-free survival of 4.5 months, compared to 9.0 months for patients without PI3K pathway activation following treatment with a Herceptin (trastuzumab) containing regimen (PMID: 21676217). 21676217
ERBB2 pos PIK3CA act mut Her2-receptor positive breast cancer sensitive Palbociclib + Pictilisib Preclinical Actionable In a preclinical study, Ibrance (palbociclib) and Pictilisib (GDC-0941) worked synergistically to inhibit survival of ERBB2 (HER2)-positive breast cancer cell lines harboring PIK3CA mutations in culture (PMID: 27020857). 27020857
ERBB2 act mut PIK3CA act mut breast cancer sensitive VS-5584 Preclinical Actionable In a preclinical study, breast cancer cells with mutations in both ERBB2 (HER2) and PIK3CA were more sensitive to VS-5584 (PMID: 23270925). 23270925
ARID1A mut PIK3CA act mut ovarian cancer sensitive GSK126 Preclinical - Cell culture Actionable In a preclinical study, expression of a constitutively active PIK3CA mutation in ARID1A-mutant ovarian cancer cell lines enhanced growth inhibition by GSK126 in culture (PMID: 25686104). 25686104
CDKN2A loss PIK3CA act mut lung squamous cell carcinoma predicted - sensitive Buparlisib + Palbociclib Preclinical - Pdx Actionable In a preclinical study, treatment with the combination of Buparlisib (BYL719) and Ibrance (palbociclib) resulted in increased tumor growth inhibition compared to either agent alone in patient-derived xenograft (PDX) models of lung squamous cell carcinoma harboring PIK3CA E542K or E545K mutations with p16 (CDKN2A) loss, including models that also had either PIK3CA amplification or PTEN loss (PMID: 30093452). 30093452
ERBB2 amp PIK3CA act mut Her2-receptor positive breast cancer decreased response Poziotinib Phase II Actionable In a Phase II trial, the presence of PIK3CA activating mutations including E542X, E545X, and H1047X correlated with shorter progression-free survival (2.66 months) compared to PIK3CA wild-type or other mutations (4.24 month, HR=1.68, p=0.033) in patients with metastatic Erbb2 (Her2)-positive (amplification or overexpression) breast cancer treated with Poziotinib (HM781-36B) (PMID: 30720867, NCT02418689). 30720867
ERBB2 over exp PIK3CA act mut Her2-receptor positive breast cancer decreased response Poziotinib Phase II Actionable In a Phase II trial, the presence of PIK3CA activating mutations including E542X, E545X, and H1047X correlated with shorter progression-free survival (2.66 months) compared to PIK3CA wild-type or other mutations (4.24 month, HR=1.68, p=0.033) in patients with metastatic Erbb2 (Her2)-positive (amplification or overexpression) breast cancer treated with Poziotinib (HM781-36B) (PMID: 30720867, NCT02418689). 30720867
PIK3CA M1043V head and neck squamous cell carcinoma sensitive Celecoxib Preclinical - Pdx Actionable In a preclinical study, Celebra (celecoxib) treatment reduced tumor growth rate in a patient-derived xenograft (PDX) model of head and neck squamous cell carcinoma harboring PIK3CA M1043V (PMID: 30683736). 30683736
PIK3CA M1043V Advanced Solid Tumor sensitive Sirolimus Preclinical Actionable In a preclinical study, Rapamune (sirolimus) inhibited proliferation in cultured cells expressing PIK3CA M1043V (PMID: 17376864). 17376864
PIK3CA M1043V head and neck squamous cell carcinoma sensitive Sulindac Preclinical - Pdx Actionable In a preclinical study, Clinoril (sulindac) treatment reduced tumor growth rate in patient-derived xenograft (PDX) models of head and neck squamous cell carcinoma harboring PIK3CA mutations, including PIK3CA M1043V (PMID: 30683736). 30683736
HRAS mut PIK3CA M1043V malignant glioma sensitive Buparlisib + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Buparlisib (BKM120) and Koselugo (selumetinib) led to a synergistic effect, resulting in growth inhibition of astrocytoma cells with an HRAS mutation and expressing PIK3CA M1043V in culture, but at a higher drug concentration compared to cells without mutant HRAS (PMID: 29975751). 29975751
BRAF V600E PIK3CA P449T colorectal cancer sensitive Pimasertib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) inhibited proliferation of colorectal cancer cells harboring BRAF V600E and PIK3CA P449T in culture (PMID: 23629727). 23629727
BRAF V600E PIK3CA P449T colorectal cancer sensitive Pimasertib + Regorafenib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) and Stivarga (regorafenib) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E and PIK3CA P449T in culture (PMID: 23629727). 23629727
BRAF V600E PIK3CA P449T colorectal cancer sensitive Pimasertib + Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) and Nexavar (sorafenib) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E and PIK3CA P449T in culture (PMID: 23629727). 23629727
BRAF V600E PIK3CA P449T colorectal cancer resistant Regorafenib Preclinical Actionable In a preclinical study, human colorectal cancer cells harboring BRAF V600E and PIK3CA P449T were resistant to Stivarga (regorafenib) in culture (PMID: 25838391). 25838391
BRAF V600E PIK3CA P449T colorectal cancer resistant Cetuximab Preclinical Actionable In a preclinical study, human colorectal cancer cells harboring BRAF V600E and PIK3CA P449T were resistant to Erbitux (cetuximab) in culture (PMID: 25838391). 25838391
BRAF V600E PIK3CA P449T colorectal cancer sensitive Cetuximab + Regorafenib Preclinical Actionable In a preclinical study, the combination of Erbitux (cetuximab) and Stivarga (regorafenib) inhibited growth, reduced Akt and Mapk phosphorylation, and induced apoptosis of human colorectal cancer cell lines harboring BRAF V600E and PIK3CA P449T in culture (PMID: 25838391). 25838391
BRAF V600E PIK3CA P449T colorectal cancer sensitive Everolimus + Pimasertib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) and Afinitor (everolimus) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E and PIK3CA P449T in culture (PMID: 23629727). 23629727
PIK3CA over exp lung squamous cell carcinoma sensitive Alpelisib Preclinical - Cell line xenograft Actionable In a preclinical study, Alpelisib (BYL719) induced apoptosis, inhibited cell proliferation, migration, and invasion of lung squamous cell carcinoma cells over expressing wild-type PIK3CA in culture, and inhibited tumor growth in cell line xenograft models (PMID: 26013318). 26013318
PIK3CA over exp lung squamous cell carcinoma sensitive Dactolisib Preclinical - Cell culture Actionable In a preclinical study, BEZ235 induced apoptosis, inhibited cell proliferation, migration, and invasion of lung squamous cell carcinoma cells over expressing wild-type Pik3ca in culture (PMID: 26013318). 26013318
PIK3CA over exp head and neck squamous cell carcinoma sensitive Gedatolisib Preclinical - Cell culture Actionable In a preclinical study, some head and neck squamous cell carcinoma cell lines over expressing PIK3CA demonstrated sensitivity to treatment with Gedatolisib (PF-05212384) (PMID: 25977343). 25977343
PIK3CA over exp lung squamous cell carcinoma sensitive Buparlisib Preclinical - Cell culture Actionable In a preclinical study, Buparlisib (BKM120) induced apoptosis, inhibited cell proliferation, migration, and invasion of lung squamous cell carcinoma cells over expressing wild-type Pik3ca in culture (PMID: 26013318). 26013318
PIK3CA over exp glioblastoma multiforme sensitive YM-024 Preclinical Actionable In a preclinical study, YM-024 inhibited proliferation and anchorage-independent growth of glioblastoma cell lines with elevated Pik3ca protein level in culture (PMID: 24718026). 24718026
PIK3CA N345I breast cancer resistant Buparlisib Preclinical - Cell culture Actionable In a preclinical study, breast cancer cells expressing PIK3CA N345I demonstrated resistance to treatment with Buparlisib (BKM120) in culture (PMID: 29636477). 29636477
ERBB2 over exp PIK3CA N345T stomach cancer predicted - resistant Trastuzumab Clinical Study - Cohort Actionable In a clinical study (AMNESIA-1), assessment of pre-treatment tumor samples from ERBB2 (HER2)-positive gastric or gastroesophageal cancer patients (defined as HER2 IHC 3+ or HER2 IHC 2+/ISH+) identified PIK3CA mutations in 15% (3/20) of patients demonstrating primary resistance to Herceptin (trastuzumab), including 1 patient harboring PIK3CA N345T (PMID: 29208673). 29208673
PIK3CA M1043I lung squamous cell carcinoma no benefit Taselisib Case Reports/Case Series Actionable In a Phase I (SWOG S1400B) trial, Taselisib (GDC-0032) treatment did not meet primary endpoint in patients with lung squamous cell carcinoma harboring PIK3CA mutations, a patients harboring PIK3CA M1043I did not demonstrated response (PMID: 31158500; NCT02785913). 31158500
PIK3CA M1043I endometrial adenocarcinoma no benefit Copanlisib Case Reports/Case Series Actionable In a Phase II (NRG-GY008) trial, Aliqopa (copanlisib) was well tolerated but demonstrated limited efficacy, resulted in stable disease in a patient with endometrioid adenocarcinoma harboring PIK3CA M1043I (PMID: 31934607). 31934607
PIK3CA amp head and neck squamous cell carcinoma predicted - sensitive Rigosertib Sodium Case Reports/Case Series Actionable In a Phase I trial, Rigosertib (ON 01910.Na) treatment resulted in a complete response with disappearance of mediastinal and lung disease in a patients with head and neck squamous cell carcinoma harboring PIK3CA amplification (Cancer Res April 15 2013 (73) (8 Supplement) LB-198). detail...
PIK3CA amp head and neck squamous cell carcinoma predicted - sensitive AZD8055 Preclinical - Cell culture Actionable In a preclinical study, treatment with AZD8055 resulted in antiproliferative activity in head and neck squamous cell carcinoma cells harboring PIK3CA amplification in culture (PMID: 28446642). 28446642
PIK3CA amp head and neck squamous cell carcinoma sensitive Radiotherapy + Taselisib Preclinical - Cell line xenograft Actionable In a preclinical study, Taselisib (GDC-0032) enhanced the effects of radiation induced apoptosis in HNSCC cell lines and cell line xenograft models with PIK3CA amplification (PMID: 26589432). 26589432
PIK3CA amp lung squamous cell carcinoma no benefit Buparlisib Preclinical - Pdx Actionable In a preclinical study, lung squamous cell carcinoma a patient-derived xenograft (PDX) model harboring PIK3CA amplification, without additional PIK3CA mutations, did not respond to Buparlisib (BKM120) treatment (PMID: 30093452). 30093452
PIK3CA amp lung squamous cell carcinoma no benefit Capivasertib Case Reports/Case Series Actionable In a Phase II trial (NLMT), Capivasertib (AZD5363) treatment resulted in no conformed response (0/12) and durable clinical benefit in 9% (1/11) of patients with squamous cell lung cancer harboring PIK3CA amplification, thus the cohort was closed due to futility (PMID: 32669708, NCT02664935). 32669708
PIK3CA amp ovarian cancer sensitive Panulisib Preclinical Actionable In a preclinical study, Panulisib (P7170) downregulated mTOR pathway signaling in ovarian cancer cells with amplified PIK3CA (PMID: 25700704). 25700704
PIK3CA amp urinary bladder cancer sensitive Gemcitabine + Pictilisib Preclinical - Pdx Actionable In a preclinical study, Pictilisib (GDC-0941) and Gemzar (gemcitabine) combination treatment resulted in inhibition of Akt phosphorylation and improved tumor growth inhibition and survival compared to single agent therapy in patient-derived xenograft (PDX) models of PIK3CA amplified bladder cancer (PMID: 28808038). 28808038
PIK3CA amp nasopharynx carcinoma sensitive MK2206 Phase II Actionable In a Phase II study, MK2206 increased stable disease to 12 months in a nasopharyngeal carcinoma patient with Pik3ca amplification (PMID: 26084990). 26084990
PIK3CA amp ovarian cancer sensitive Voxtalisib Preclinical - Cell line xenograft Actionable In a preclinical study, an ovarian cancer cell line harboring PIK3CA E545K was sensitive to XL765 (SAR245409), demonstrating inhibition of cell proliferation in culture, and inhibition of tumor growth in cell line xenograft models (PMID: 24634413). 24634413
PIK3CA amp lung non-small cell carcinoma predicted - sensitive Sulindac Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cell lines harboring either a PIK3CA mutation or PIK3CA amplification demonstrated increased sensitivity to Clinoril (sulindac) compared to cell lines with wild-type PIK3CA, resulting in decreased proliferation in culture (PMID: 30683736). 30683736
PIK3CA amp ovarian cancer sensitive XL147 Preclinical - Cell line xenograft Actionable In a preclinical study, XL147 inhibited PI3K signaling and proliferation of a PIK3CA amplified human ovarian cancer cell line in culture, and inhibited tumor growth in xenograft models (PMID: 25637314). 25637314
PIK3CA amp triple-receptor negative breast cancer sensitive Linsitinib + Pictilisib Preclinical - Cell culture Actionable In a preclinical study, Linsitinib (OSI-906) enhanced sensitivity of PIK3CA amplified triple-receptor negative breast cancer cells to Pictilisib (GDC-0941) in culture (PMID: 27196766). 27196766
PIK3CA amp head and neck squamous cell carcinoma sensitive Dactolisib Preclinical - Cell culture Actionable In a preclinical study, BEZ235 resulted in antiproliferative activity in head and neck squamous cell carcinoma cells harboring PIK3CA amplification in culture (PMID: 28446642). 28446642
PIK3CA amp triple-receptor negative breast cancer sensitive NVP-AEW541 + Pictilisib Preclinical - Cell culture Actionable In a preclinical study, NVP-AEW541 enhanced sensitivity of PIK3CA amplified triple-receptor negative breast cancer cells to Pictilisib (GDC-0941) in culture (PMID: 27196766). 27196766
PIK3CA E545K PIK3CA amp lung squamous cell carcinoma predicted - sensitive Buparlisib Preclinical - Cell line xenograft Actionable In a preclinical study, Buparlisib (BKM120) treatment resulted in inhibition of AKT and S6 phosphorylation and durable responses in 2 of 3 lung squamous cell carcinoma patient-derived xenograft (PDX) models harboring PIK3CA E545K and PIK3CA amplification (PMID: 30093452). 30093452
CDKN2A loss PIK3CA E545K PIK3CA amp lung squamous cell carcinoma sensitive Buparlisib + Palbociclib Preclinical - Pdx Actionable In a preclinical study, treatment with the combination of Buparlisib (BYL719) and Ibrance (palbociclib) resulted in increased tumor growth inhibition compared to either agent alone in patient-derived xenograft (PDX) models of lung squamous cell carcinoma harboring PIK3CA E545K and PIK3CA amplification, with p16 (CDKN2A) loss (PMID: 30093452). 30093452
ERBB2 pos PIK3CA amp Her2-receptor positive breast cancer predicted - sensitive Neratinib Phase III Actionable In a Phase III trial (ExteNET), Nerlynx (neratinib) treatment resulted in improved 5-year invasive disease-free survival (92.4% vs 84.5%, HR=0.41, p=0.028) and clinical benefit (HR=0.40, p=0.041) compared to placebo in patients with ERBB2 (HER2)-positive early breast cancer who completed trastuzumab-based adjuvant therapy, and harbored PIK3CA amplification (n=61) or mutations (n=210), including H1047R (n=110), E542K (n=18), and E545K/D (n=82) (PMID: 30867034; NCT00878709). 30867034
PIK3CA P447_L455del estrogen-receptor positive breast cancer predicted - sensitive Alpelisib + Letrozole Case Reports/Case Series Actionable In a clinical case study, a patient with estrogen-receptor positive breast cancer harboring PIK3CA P447_L455del demonstrated an 11 month sustained response to the combination therapy of Femara (letrozole) and Alpelisib (BYL719) (PMID: 29284706). 29284706
PIK3CA Q1033R PIK3CA H1047R Burkitt lymphoma predicted - sensitive Idelalisib Case Reports/Case Series Actionable In a clinical case study, Zydelig (idelalisib) treatment resulted in tumor shrinkage and decreased plasma LDH that continued for 10 months before recurrence in a patient with relapsed Burkitt lymphoma harboring PIK3CA H1047R and PIK3CA Q1033R (PMID: 32193631). 32193631
PIK3CA E542V colorectal cancer predicted - sensitive Cetuximab Case Reports/Case Series Actionable In a retrospective analysis, Erbitux (cetuximab) treatment resulted in stable disease in a colorectal carcinoma patient harboring a PIK3CA E542V mutation (PMID: 25714871). 25714871
ERBB2 over exp PIK3CA H1047R Her2-receptor positive breast cancer sensitive Buparlisib + Trastuzumab Preclinical Actionable In a preclinical study, the combination of Herceptin (trastuzumab) and Buparlisib (BKM120) inhibited tumor growth in mouse ERBB2 (HER2)-over expressing breast cancer models expressing PIK3CA H1047R, with moderate efficacy over Buparlisib (BKM120) alone (PMID: 23940356). 23940356
ERBB2 over exp PIK3CA H1047R Her2-receptor positive breast cancer no benefit Buparlisib + Lapatinib + Trastuzumab Preclinical Actionable In a preclinical study, the combination of Buparlisib (BKM120), Herceptin (trastuzumab), and Tykerb (lapatinib) inhibited tumor growth in mouse models of ERBB2 (HER2)-over expressing breast cancer expressing PIK3CA H1047R, but efficacy was not significantly improved over Buparlisib (BKM120) alone (PMID: 23940356). 23940356
ERBB2 over exp PIK3CA H1047R Her2-receptor positive breast cancer resistant Pertuzumab + Trastuzumab Preclinical Actionable In a preclinical study, a mouse breast cancer model with ERBB2 (HER2) over-expression that also expressed the PIK3CA H1047R mutation showed resistance to the combination of Heceptin (trastuzumab) and Perjeta (pertuzumab) (PMID: 23940356). 23940356
ERBB2 over exp PIK3CA H1047R stomach cancer predicted - resistant Trastuzumab Clinical Study - Cohort Actionable In a clinical study (AMNESIA-1), assessment of pre-treatment tumor samples from ERBB2 (HER2)-positive gastric or gastroesophageal cancer patients (defined as HER2 IHC 3+ or HER2 IHC 2+/ISH+) identified PIK3CA mutations in 15% (3/20) of patients demonstrating primary resistance to Herceptin (trastuzumab), including 1 patient harboring PIK3CA H1047R (PMID: 29208673). 29208673
ERBB2 over exp PIK3CA H1047R Her2-receptor positive breast cancer resistant Trastuzumab Preclinical Actionable In a preclinical study, mouse breast cancer models over expressing ERBB2 (HER2) and expressing PIK3CA H1047R were resistant to Herceptin (trastuzumab) (PMID: 23940356). 23940356
ERBB2 over exp PIK3CA H1047R Her2-receptor positive breast cancer sensitive Buparlisib + Pertuzumab + Trastuzumab Preclinical Actionable In a preclinical study, the combination of Buparlisib (BKM120), Herceptin (trastuzumab), and Perjeta (pertuzumab) inhibited tumor growth in mouse models of ERBB2 (HER2)-over expressing breast cancer expressing PIK3CA H1047R, with improved efficacy over Buparlisib (BKM120) alone (PMID: 23940356). 23940356
ERBB2 over exp PIK3CA H1047R Her2-receptor positive breast cancer resistant Lapatinib + Trastuzumab Preclinical Actionable In a preclinical study, a mouse breast cancer model with mammary ERBB2 (HER2) over-expression that also expressed the PIK3CA H1047R mutation showed resistance to the combination of Herceptin (trastuzumab) and Tykerb (lapatinib) (PMID: 23940356). 23940356
ERBB2 over exp PIK3CA H1047R Her2-receptor positive breast cancer sensitive Bevacizumab + Buparlisib Preclinical Actionable In a preclinical study, treatment with Buparlisib (BKM120) resulted in decreased tumor growth, but not tumor regression, in mouse models of ERBB2 (HER2)-over expressing breast cancer expressing PIK3CA H1047R (PMID: 23940356). 23940356
PIK3CA H1047R breast cancer sensitive Buparlisib Preclinical - Cell line xenograft Actionable In a preclinical study, a breast cancer cell line xenograft model harboring PIK3CA H1047R demonstrated tumor regression within the mammary fat pad when treated with Buparlisib (BKM120) (PMID: 28539475). 28539475
PIK3CA H1047R breast cancer sensitive M2698 Preclinical - Cell line xenograft Actionable In a preclinical study, a breast cancer xenograft model harboring PIK3CA H1047R was sensitive to M2698 (MSC2363318A), demonstrating inhibition of tumor growth (PMID: 27186432). 27186432
PIK3CA H1047R transitional cell carcinoma no benefit Buparlisib Case Reports/Case Series Actionable In a Phase II trial, Buparlisib (BKM120) treatment resulted in progressive disease in a patient with metastatic urothelial carcinoma harboring PIK3CA H1047R (PMID: 32767682; NCT01551030). 32767682
PIK3CA H1047R ovarian cancer sensitive AZD8835 Preclinical Actionable In a preclinical study, AZD8835 inhibited tumor growth in mouse xenografts of ovarian cancer with a Pik3ca H1047R mutation (AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2830). detail...
PIK3CA H1047R colorectal cancer sensitive Metformin Preclinical - Cell line xenograft Actionable In a preclinical study, Glucophage (metformin) demonstrated efficacy in treating dietary restriction-resistant human colorectal cancer cell line xenograft tumors harboring PIK3CA H1047R (PMID: 23986086). 23986086
PIK3CA H1047R thyroid gland cancer sensitive MK2206 Preclinical - Cell culture Actionable In a preclinical study, MK2206 inhibited AKT activation, proliferation, and growth of thyroid cancer cell lines with PI3K/AKT pathway alterations in culture, including an anaplastic thyroid cancer cell line harboring PIK3CA H1047R (PMID: 21289267). 21289267
PIK3CA H1047R breast cancer sensitive Dactolisib Preclinical Actionable In a preclinical study, BEZ235 inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA H1047R in culture (PMID: 26627007). 26627007
PIK3CA H1047R colorectal cancer sensitive Cetuximab Case Reports/Case Series Actionable In a retrospective analysis, Erbitux (cetuximab) combined with radiation therapy resulted in stable disease for 6 months in a colorectal carcinoma patient harboring a PIK3CA H1047R mutation (PMID: 25714871). 25714871
PIK3CA H1047R Advanced Solid Tumor predicted - sensitive Alpelisib Preclinical - Cell culture Actionable In a preclinical study, Piqray (Alpelisib) decreased Akt phosphorylation and inhibited PI3K signaling, and demonstrated dose-dependent inhibition of survival in human pluripotent stem cells harboring PIK3CA H1047R in culture (PMID: 30948643). 30948643
PIK3CA H1047R urinary bladder cancer sensitive Pictilisib Preclinical - Pdx Actionable In a preclinical study, Pictilisib (GDC-0941) inhibited Akt phosphorylation and tumor growth, prolonged survival in patient-derived xenograft (PDX) models of bladder cancer harboring PIK3CA H1047R (PMID: 28808038). 28808038
PIK3CA H1047R breast cancer sensitive CH5132799 Preclinical Actionable In a preclinical study, CH5132799 inhibited proliferation of breast cancer cells harboring PIK3CA H1047R in culture (PMID: 21558396). 21558396
PIK3CA H1047R urinary bladder cancer sensitive Dactolisib Preclinical - Pdx Actionable In a preclinical study, BEZ235 inhibited tumor growth in a patient-derived xenograft (PDX) model of bladder cancer harboring PIK3CA H1047R (PMID: 26270481). 26270481
PIK3CA H1047R Advanced Solid Tumor sensitive Sirolimus Preclinical Actionable In a preclinical study, transformed cells expressing PIK3CA H1047R were sensitive to Rapamune (sirolimus), resulting in inhibition of transformation in culture (PMID: 15647370). 15647370
PIK3CA H1047R breast cancer sensitive Taselisib Phase I Actionable In a Phase I trial, four patients with breast cancer harboring PIK3CA H1047R demonstrated a confirmed partial response when treated with Taselisib (GDC-0032) (PMID: 28331003). 28331003
PIK3CA H1047R stomach cancer sensitive Capivasertib Preclinical - Pdx Actionable In a preclinical study, AZD5363 inhibited growth in a patient-derived xenograft model of gastric cancer harboring a PIK3CA H1047R mutation (PMID: 24088382). 24088382
PIK3CA H1047R breast cancer sensitive Gedatolisib Preclinical Actionable In a preclinical study, Gedatolisib (PKI-587) inhibited growth of human breast cancer cells harboring PIK3CA H1047R in culture (PMID: 21325073, PMID: 17314276). 17314276 21325073
PIK3CA H1047R oral squamous cell carcinoma resistant Palbociclib Preclinical - Cell culture Actionable In a preclinical study, oral squamous cell carcinoma cells expressing PIK3CA H1047R demonstrated resistance to Ibrance (palbociclib) treatment in culture (PMID: 31516747). 31516747
PIK3CA H1047R colorectal cancer resistant Cetuximab + Fluorouracil Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells over expressing PIK3CA H1047R were resistant to Erbitux (cetuximab) and Fluorouracil combination treatment in culture (PMID: 28424201). 28424201
PIK3CA H1047R lung cancer no benefit Sirolimus Preclinical Actionable In a preclinical study, Sirolimus (rapamycin) did not induce tumor shrinkage in mouse lung cancer models carrying PIK3CA H1047R (PMID: 19029981). 19029981
PIK3CA H1047R lung cancer sensitive Dactolisib Preclinical Actionable In a preclinical study, BEZ235 reduced tumor size in mouse models of lung cancer carrying PIK3CA H1047R (PMID: 19029981). 19029981
PIK3CA H1047R lung squamous cell carcinoma no benefit Taselisib Case Reports/Case Series Actionable In a Phase I (SWOG S1400B) trial, Taselisib (GDC-0032) treatment did not meet primary endpoint in patients with lung squamous cell carcinoma harboring PIK3CA mutations, none of the 4 patients harboring PIK3CA H1047R demonstrated response (PMID: 31158500; NCT02785913). 31158500
PIK3CA H1047R breast cancer sensitive DHM25 Preclinical - Cell culture Actionable In a preclinical study, DHM25 increased cell death in breast cancer cell lines harboring PIK3CA H1047R in culture (PMID: 26237138). 26237138
PIK3CA H1047R estrogen-receptor positive breast cancer predicted - sensitive Everolimus Clinical Study - Cohort Actionable In a retrospective analysis, combination of Afinitor (everolimus) and hormone therapy resulted in improved median progression-free survival (8.8 vs 4.1 months, p=0.02) in patients with hormone receptor-positive metastatic breast cancer harboring PIK3CA H1047R (n=6) compared to patients without PIK3CA H1047R (n=10) (PMID: 31088410). 31088410
PIK3CA H1047R breast cancer sensitive BAY1125976 Preclinical - Cell line xenograft Actionable In a preclinical study, BAY1125976 inhibited proliferation of breast cancer cell lines harboring PIK3CA H1047R in culture, and inhibited AKT signaling and tumor growth in a PIK3CA H1047R-mutant cell line xenograft model (PMID: 27699769). 27699769
PIK3CA H1047R lung squamous cell carcinoma sensitive Alpelisib Preclinical - Cell culture Actionable In a preclinical study, Alpelisib (BYL719) induced apoptosis, inhibited cell proliferation, migration, and invasion of lung squamous cell carcinoma cells over expressing PIK3CA H1047R in culture (PMID: 26013318). 26013318
PIK3CA H1047R breast metaplastic carcinoma predicted - sensitive Buparlisib + Paclitaxel Case Reports/Case Series Actionable In a clinical case study, Buparlisib (BKM120) in combination with Taxol (paclitaxel) resulted in a durable partial response in a patient with breast metaplastic carcinoma harboring PIK3CA H1047R, with a total response period of 70 weeks and an overall survival of 42 months (PMID: 30577988). 30577988
PIK3CA H1047R head and neck squamous cell carcinoma sensitive Sirolimus + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, Rapamune (sirolimus) worked synergistically with Mekinist (trametinib) to inhibit proliferation of head and neck squamous carcinoma cell lines harboring PIK3CA H1047R in culture and to reduce tumor growth in cell line xenograft models (PMID: 26882569). 26882569
PIK3CA H1047R lung adenocarcinoma sensitive Dactolisib Preclinical Actionable In a preclinical study, BEZ235 promoted tumor regression in a mouse lung adenocarcinoma model expressing PIK3CA H1047R (PMID: 19029981). 19029981
PIK3CA H1047R head and neck squamous cell carcinoma sensitive Gedatolisib Preclinical - Cell culture Actionable In a preclinical study, head and neck squamous cell carcinoma cell lines harboring PIK3CA H1047R demonstrated sensitivity to treatment with Gedatolisib (PF-05212384) in culture (PMID: 25977343). 25977343
PIK3CA H1047R Advanced Solid Tumor sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited survival of transformed cell lines overexpressing PIK3CA H1047R in culture (PMID: 26627007). 26627007
PIK3CA H1047R head and neck squamous cell carcinoma predicted - sensitive SHR-A1307 Preclinical - Cell culture Actionable In a preclinical study, head and neck squamous cell carcinoma cells harboring PIK3CA H1047R treated with SHR-A1307 demonstrated inhibition of cell growth in culture (PMID: 30962319). 30962319
PIK3CA H1047R breast cancer sensitive Metformin Preclinical - Cell line xenograft Actionable In a preclinical study, Glucophage (metformin) inhibited cell proliferation of a dietary restriction-resistant PIK3CA H1047R-harboring human breast cancer cell line in culture, and inhibited tumor growth in xenograft models (PMID: 23986086). 23986086
PIK3CA H1047R lung squamous cell carcinoma sensitive Dactolisib Preclinical - Cell culture Actionable In a preclinical study, BEZ235 induced apoptosis, inhibited cell proliferation, migration, and invasion of lung squamous cell carcinoma cells over expressing PIK3CA H1047R in culture (PMID: 26013318). 26013318
PIK3CA H1047R breast cancer sensitive CYH33 Preclinical - Cell line xenograft Actionable In a preclinical study, CYH33 inhibited proliferation of breast cancer cell lines harboring PIK3CA H1047R in culture, inhibited tumor progression in a transgenic mouse model, and induced cell cycle arrest, and inhibited PI3K signaling and tumor growth in cell line xenograft models (PMID: 30003928). 30003928
PIK3CA H1047R urinary bladder cancer sensitive Cisplatin + Pictilisib Preclinical - Pdx Actionable In a preclinical study, combination of or sequential treatment with Pictilisib (GDC-0941) and Platinol (cisplatin) significantly delayed tumor growth and prolonged survival in patient-derived xenograft (PDX) models of bladder cancer harboring PIK3CA H1047R (PMID: 28808038). 28808038
PIK3CA H1047R ovarian cancer sensitive PF-04691502 Preclinical - Cell line xenograft Actionable In a preclinical study, PF-04691502 inhibited Pi3k signaling, resulted in growth inhibition of ovarian cancer cells harboring PIK3CA H1047R in culture and in cell line xenograft models (PMID: 21750219). 21750219
PIK3CA H1047R breast cancer sensitive Miransertib Preclinical - Cell culture Actionable In a preclinical study, a breast cancer cell line harboring PIK3CA H1047R demonstrated sensitivity to treatment with Miransertib (ARQ092) in culture, resulting in inhibition of cell proliferation (PMID: 26469692). 26469692
PIK3CA H1047R progesterone-receptor positive breast cancer predicted - sensitive Everolimus Clinical Study - Cohort Actionable In a retrospective analysis, combination of Afinitor (everolimus) and hormone therapy resulted in improved median progression-free survival (8.8 vs 4.1 months, p=0.02) in patients with hormone receptor-positive metastatic breast cancer harboring PIK3CA H1047R (n=6) compared to patients without PIK3CA H1047R (n=10) (PMID: 31088410). 31088410
PIK3CA H1047R breast cancer sensitive Lapatinib Preclinical Actionable In a preclinical study, Tykerb (lapatinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA H1047R in culture (PMID: 26627007). 26627007
PIK3CA H1047R lung squamous cell carcinoma sensitive Buparlisib Preclinical - Cell culture Actionable In a preclinical study, Buparlisib (BKM120) induced apoptosis, inhibited cell proliferation, migration, and invasion of lung squamous cell carcinoma cells over expressing wild-type Pik3ca in culture (PMID: 26013318). 26013318
PIK3CA H1047R head and neck squamous cell carcinoma resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, head and neck squamous cell carcinoma cells harboring PIK3CA H1047R were resistant to Erbitux (cetuximab) in culture (PMID: 30962319). 30962319
PIK3CA H1047R breast cancer sensitive Borussertib Preclinical - Cell culture Actionable In a preclinical study, borussertib inhibited proliferation of a breast cancer cell line harboring PIK3CA H1047R in culture (PMID: 30858154). 30858154
PIK3CA H1047R ovarian cancer sensitive A66 Preclinical - Cell line xenograft Actionable In a preclinical study, A66 delayed tumor growth in an ovarian cancer cell line xenograft model harboring PIK3CA H1047R (PMID: 21668414). 21668414
PIK3CA H1047R malignant glioma sensitive Buparlisib + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Buparlisib (BKM120) and Koselugo (selumetinib) led to a synergistic effect, resulting in growth inhibition of astrocytoma cells expressing PIK3CA H1047R, but did not result in an effect as high as that seen in cells expressing PIK3CA R88Q or PIK3CA E542K in culture (PMID: 29975751). 29975751
PIK3CA H1047R Her2-receptor negative breast cancer no benefit Everolimus Phase III Actionable In a retrospective analysis of a Phase III trial (BOLERO-2), Afinitor (everolimus) demonstrated comparable progression-free survival benefit in patients with hormone receptor-positive, Erbb2 (Her2)-negative breast cancer harboring wild-type (HR=0.43) or mutant (HR=0.37) PIK3CA, similar benefit was observed in subgroups harboring PIK3CA H1047R (HR=0.37) and PIK3CA E545K/E542K (HR=0.30) (PMID: 28183140; NCT00863655). 28183140
PIK3CA H1047R head and neck squamous cell carcinoma predicted - sensitive Sulindac Preclinical - Cell culture Actionable In a preclinical study, head and neck squamous cell carcinoma cell lines harboring PIK3CA H1047R demonstrated increased sensitivity to Clinoril (sulindac) compared to cell lines with wild-type PIK3CA, resulting in decreased proliferation in culture (PMID: 30683736). 30683736
PIK3CA H1047R ovarian cancer sensitive CH5132799 Phase I Actionable In a Phase I trial, CH5132799 demonstrated safety and preliminary efficacy in patients with advanced solid tumors, including a partial response in a patient with ovarian cancer harboring PIK3CA H1047R (PMID: 25231405). 25231405
PIK3CA H1047R breast cancer sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA H1047R in culture (PMID: 26627007). 26627007
PIK3CA H1047R Advanced Solid Tumor sensitive Rigosertib Sodium Preclinical - Cell culture Actionable In a preclinical study, Rigosertib (ON 01910.Na) inhibited oncogenic transformation in fibroblast cells over-expressing Pik3ca H1047R in culture (PMID: 27104980). 27104980
PIK3CA H1047R breast cancer sensitive ARQ 751 Preclinical - Cell culture Actionable In a preclinical study, a breast cancer cell line harboring PIK3CA H1047R demonstrated sensitivity to treatment with ARQ 751 in culture, resulting in inhibition of cell proliferation (PMID: 26469692). 26469692
PIK3CA H1047R colon cancer sensitive T-2143 Preclinical - Cell line xenograft Actionable In a preclinical study, T-2143 treatment inhibited Akt phosphorylation and proliferation of colon cancer cells harboring PIK3CA H1047R in culture, and inhibited tumor growth in a cell line xenograft model (PMID: 32499300). 32499300
PIK3CA H1047R head and neck squamous cell carcinoma sensitive Radiotherapy + Taselisib Preclinical Actionable In a preclinical study, Taselisib (GDC-0032) enhanced the effects of radiation induced apoptosis of head and neck squamous carcinoma cells harboring PIK3CA H1047R (PMID: 26589432). 26589432
PIK3CA H1047R Advanced Solid Tumor sensitive A66 Preclinical Actionable In a preclinical study, A66 delayed tumor growth in human tumor xenograft models harboring PIK3CA H1047R mutations (PMID: 21668414). 21668414
PIK3CA H1047R oral squamous cell carcinoma decreased response Ribociclib Preclinical - Cell culture Actionable In a preclinical study, oral squamous cell carcinoma cells expressing PIK3CA H1047R demonstrated reduced sensitivity to Kisqali (ribociclib) treatment compared to cells expressing wild-type PIK3CA in culture (PMID: 31516747). 31516747
PIK3CA H1047R thyroid gland cancer sensitive MK2206 + Temsirolimus Preclinical - Cell culture Actionable In a preclinical study, MK2206 and Torisel (temsirolimus) demonstrated synergy in inhibiting growth of an anaplastic thyroid cancer cell line harboring PIK3CA H1047R in culture (PMID: 21289267). 21289267
PIK3CA H1047R breast cancer sensitive Alpelisib Preclinical Actionable In a preclinical study, Alpelisib (BYL719) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA H1047R in culture (PMID: 26627007). 26627007
PIK3CA H1047R breast cancer sensitive MK2206 Preclinical Actionable In a preclinical study, MK2206 inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA H1047R in culture (PMID: 26627007). 26627007
PIK3CA H1047R lung adenocarcinoma no benefit Sirolimus Preclinical Actionable In a preclinical study, Sirolimus (rapamycin) failed to inhibit tumor growth in a mouse lung adenocarcinoma model expressing the PIK3CA H1047R mutation (PMID: 19029981). 19029981
PIK3CA H1047R oral squamous cell carcinoma decreased response Abemaciclib Preclinical - Cell culture Actionable In a preclinical study, oral squamous cell carcinoma cells expressing PIK3CA H1047R demonstrated reduced sensitivity to Verzenio (abemaciclib) treatment compared to cells expressing wild-type PIK3CA in culture (PMID: 31516747). 31516747
PIK3CA H1047R breast cancer sensitive Neratinib Preclinical Actionable In a preclinical study, Nerlynx (neratinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA H1047R in culture (PMID: 26627007). 26627007
ERBB2 amp PIK3CA H1047R breast cancer sensitive CH5132799 + Trastuzumab Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of CH5132799 and Herceptin (trastuzumab) inhibited tumor growth and overcame Herceptin (trastuzumab) insensitivity in xenograft models of a human breast cancer cell line harboring PIK3CA H1047R and ERBB2 (HER2) amplification (PMID: 21558396). 21558396
ERBB2 amp PIK3CA H1047R ovarian cancer sensitive CH5132799 Preclinical - Cell line xenograft Actionable In a preclinical study, CH5132799 inhibited cell growth in a human ovarian cancer cell line harboring PIK3CA H1047R and ERBB2 (HER2) amplification, and inhibited tumor growth in xenograft models (PMID: 21558396). 21558396
ERBB2 amp PIK3CA H1047R breast cancer sensitive Gedatolisib Preclinical Actionable In a preclinical study, Gedatolisib (PKI-587) inhibited growth of human breast cancer cells harboring ERBB2 (HER2) amplification and PIK3CA H1047R in culture (PMID: 21325073, PMID: 17314276). 17314276 21325073
ERBB2 amp PIK3CA H1047R breast cancer sensitive CYH33 Preclinical - Cell culture Actionable In a preclinical study, CYH33 inhibited proliferation of breast cancer cell lines harboring PIK3CA H1047R and ERBB2 (HER2) amplification in culture (PMID: 30003928). 30003928
ERBB2 amp PIK3CA H1047R breast cancer sensitive CH5132799 Preclinical - Cell line xenograft Actionable In a preclinical study, CH5132799 inhibited cell growth and Akt phosphorylation, and promoted apoptosis in a human breast cancer cell line harboring PIK3CA H1047R and ERBB2 (HER2) amplification, and inhibited tumor growth in xenograft models (PMID: 21558396). 21558396
ERBB2 over exp PIK3CA H1047R SRC over exp urinary bladder cancer no benefit Ponatinib Preclinical - Pdx Actionable In a preclinical study, treatment with Iclusig (ponatinib) was not effective in inhibiting tumor growth in a patient-derived xenograft (PDX) model of bladder cancer with SRC over expression, which also over expressed ERBB2 (HER2) and harbored PIK3CA H1047R (PMID: 26270481). 26270481
ERBB2 over exp PIK3CA H1047R SRC over exp urinary bladder cancer no benefit Lapatinib Preclinical - Pdx Actionable In a preclinical study, treatment with Tykerb (lapatinib) was not effective in inhibiting tumor growth in a patient-derived xenograft (PDX) model of bladder cancer with ERBB2 (HER2) over expression, which also over expressed SRC and harbored PIK3CA H1047R (PMID: 26270481). 26270481
ERBB2 pos PIK3CA H1047R Her2-receptor positive breast cancer sensitive Ado-trastuzumab emtansine Preclinical - Cell line xenograft Actionable In a preclinical study, Kadcyla (trastuzumab emtansine) inhibited survival of Herceptin (trastuzumab)-resistant ERBB2 (HER2) positive breast cancer cells harboring PIK3CA H1047R in culture, and induced tumor regression in cell line xenograft models (PMID: 26920887). 26920887
ERBB2 pos PIK3CA H1047R Her2-receptor positive breast cancer predicted - sensitive Neratinib Phase III Actionable In a Phase III trial (ExteNET), Nerlynx (neratinib) treatment resulted in improved 5-year invasive disease-free survival (92.4% vs 84.5%, HR=0.41, p=0.028) and clinical benefit (HR=0.40, p=0.041) compared to placebo in patients with ERBB2 (HER2)-positive early breast cancer who completed trastuzumab-based adjuvant therapy, and harbored PIK3CA amplification (n=61) or mutations (n=210), including H1047R (n=110), E542K (n=18), and E545K/D (n=82) (PMID: 30867034; NCT00878709). 30867034
BRAF V600E PIK3CA H1047R colorectal cancer predicted - sensitive MK2206 Preclinical - Cell line xenograft Actionable In a preclinical study, MK2206 treatment resulted in a modest tumor growth inhibition in a cell line xenograft model of colorectal cancer harboring BRAF V600E and PIK3CA H1047R (PMID: 22180495). 22180495
BRAF V600E PIK3CA H1047R colorectal cancer resistant Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, Zelboraf (vemurafenib) treatment did not inhibit proliferation of colorectal cancer cells harboring BRAF V600E and PIK3CA H1047R in culture, and did not inhibit tumor growth in a cell line xenograft model (PMID: 22180495). 22180495
BRAF V600E PIK3CA H1047R thyroid gland carcinoma resistant Everolimus Case Reports/Case Series Actionable In a clinical case study, a patient with anaplastic thyroid carcinoma co-harboring BRAF V600E and PIK3CA H1047R demonstrated resistance to treatment with Afinitor (everolimus) (PMID: 27797976). 27797976
BRAF V600E PIK3CA H1047R thyroid gland carcinoma predicted - sensitive Dabrafenib + Everolimus + Trametinib Case Reports/Case Series Actionable In a clinical case study, a patient with anaplastic thyroid carcinoma co-harboring BRAF V600E and PIK3CA H1047R demonstrated tumor regression when treated with the triple combination, Tafinlar (dabrafenib), Mekinist (trametinib), and Afinitor (everolimus) (PMID: 27797976). 27797976
BRAF V600E PIK3CA H1047R thyroid gland carcinoma resistant Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, a patient with anaplastic thyroid carcinoma co-harboring BRAF V600E and PIK3CA H1047R demonstrated resistance to the combination therapy, Mekinist (trametinib) and Tafinlar (dabrafenib) (PMID: 27797976). 27797976
BRAF V600E PIK3CA H1047R colorectal cancer sensitive MK2206 + Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, Zelboraf (vemurafenib) treatment in combination with MK2206 induced apoptosis and synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E and PIK3CA H1047R in culture, and inhibited tumor growth in a cell line xenograft model (PMID: 22180495). 22180495
AKT1 over exp PIK3CA H1047R breast cancer resistant Alpelisib Preclinical - Cell culture Actionable In a preclinical study, Akt1 over expression in breast cancer cells harboring PIK3CA H1047R resulted in resistance to Alpelisib (BYL719) in culture (PMID: 27604488). 27604488
NRAS mut PIK3CA H1047R melanoma predicted - resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, one of two NRAS-mutant melanoma cell lines expressing PIK3CA H1047R demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 30819666). 30819666
PIK3CA E726K PIK3CA H1047R breast cancer sensitive Everolimus Preclinical - Cell culture Actionable In a preclinical study, breast epithelial cells expressing PIK3CA E726K and PIK3CA H1047R in cis demonstrated increased sensitivity to growth inhibition by Afinitor (everolimus) treatment compared to cells expressing individual PIK3CA mutations in culture (PMID: 31699932). 31699932
PIK3CA E726K PIK3CA H1047R breast cancer sensitive Alpelisib Preclinical - Cell culture Actionable In a preclinical study, breast epithelial cells expressing PIK3CA E726 and PIK3CA H1047R in cis demonstrated increased sensitivity to growth inhibition by Piqray (Alpelisib) treatment compared to cells expressing individual PIK3CA mutations in culture, while cells expressing PIK3CA E726 and PIK3CA H1047R in trans did not (PMID: 31699932). 31699932
PIK3CA E726K PIK3CA H1047R breast cancer sensitive GDC-0077 Preclinical - Cell culture Actionable In a preclinical study, breast epithelial cells expressing PIK3CA E726K and PIK3CA H1047R in cis demonstrated increased sensitivity to growth inhibition by GDC-0077 treatment compared to cells expressing individual PIK3CA mutations in culture (PMID: 31699932). 31699932
ERBB2 G776V PIK3CA H1047R ovarian cancer resistant Neratinib Preclinical - Cell culture Actionable In a preclinical study, expression of PIK3CA H1047R conferred resistance to Nerlynx (neratinib) in an ovarian cancer cell line harboring ERBB2 (HER2) G776V in culture (PMID: 31978326). 31978326
ERBB2 G776V PIK3CA H1047R ovarian cancer sensitive Everolimus + Neratinib Preclinical - Cell culture Actionable In a preclinical study, the addition of Afinitor (everolimus) to treatment with Nerlynx (neratinib) inhibited viability of an ovarian cancer cell line harboring ERBB2 (HER2) G776V and expressing PIK3CA H1047R in culture (PMID: 31978326). 31978326
ERBB2 G778_P780dup PIK3CA H1047R breast cancer decreased response Neratinib Preclinical - Pdx Actionable In a preclinical study, Nerlynx (neratinib) resulted in a moderate delay of tumor growth in a breast cancer patient-derived xenograft model harboring ERBB2 (HER2) G778_P780dup and PIK3CA H1074R (PMID: 31978326). 31978326
ERBB2 V777L PIK3CA H1047R breast cancer sensitive Everolimus + Neratinib Preclinical - Cell culture Actionable In a preclinical study, Afinitor (everolimus) and Nerlynx (neratinib) worked synergistically to inhibit viability of a breast cancer cell line harboring ERBB2 (HER2) V777L and PIK3CA H1047R in culture (PMID: 31978326). 31978326
ERBB2 V777L PIK3CA H1047R breast cancer resistant Neratinib Preclinical - Cell culture Actionable In a preclinical study, a breast cancer cell line harboring ERBB2 (HER2) V777L and PIK3CA H1047R demonstrated resistance to Nerlynx (neratinib) in culture (PMID: 31978326). 31978326
ERBB2 L755S PIK3CA H1047R breast cancer sensitive Everolimus + Neratinib Preclinical - Cell culture Actionable In a preclinical study, Afinitor (everolimus) and Nerlynx (neratinib) worked synergistically to inhibit viability of a breast cancer cell line harboring ERBB2 (HER2) L755S and PIK3CA H1047R in culture (PMID: 31978326). 31978326
ERBB2 L755S PIK3CA H1047R breast cancer resistant Neratinib Preclinical - Cell culture Actionable In a preclinical study, a breast cancer cell line harboring ERBB2 (HER2) L755S and PIK3CA H1047R demonstrated resistance to Nerlynx (neratinib) in culture (PMID: 31978326). 31978326
PIK3CA E545X endometrial adenocarcinoma no benefit Copanlisib Case Reports/Case Series Actionable In a Phase II (NRG-GY008) trial, Aliqopa (copanlisib) was well tolerated but demonstrated limited efficacy, resulted in progressive disease in a patient with endometrioid adenocarcinoma harboring a PIK3CA E545 mutation, and progressive disease in a patient with serous endometrial adenocarcinoma harboring a PIK3CA E545 mutation (PMID: 31934607). 31934607
ERBB2 over exp PIK3CA E545X Her2-receptor positive breast cancer decreased response Poziotinib Phase II Actionable In a Phase II trial, the presence of PIK3CA activating mutations including E542X, E545X, and H1047X correlated with shorter progression-free survival (2.66 months) compared to PIK3CA wild-type or other mutations (4.24 month, HR=1.68, p=0.033) in patients with metastatic Erbb2 (Her2)-positive (amplification or overexpression) breast cancer treated with Poziotinib (HM781-36B) (PMID: 30720867, NCT02418689). 30720867
ERBB2 amp PIK3CA E545X Her2-receptor positive breast cancer decreased response Poziotinib Phase II Actionable In a Phase II trial, the presence of PIK3CA activating mutations including E542X, E545X, and H1047X correlated with shorter progression-free survival (2.66 months) compared to PIK3CA wild-type or other mutations (4.24 month, HR=1.68, p=0.033) in patients with metastatic Erbb2 (Her2)-positive (amplification or overexpression) breast cancer treated with Poziotinib (HM781-36B) (PMID: 30720867, NCT02418689). 30720867
PIK3CA G118D lung non-small cell carcinoma sensitive LY3023414 Preclinical - Cell line xenograft Actionable In a preclinical study, LY3023414 inhibited proliferation of non-small cell lung cancer cells harboring PIK3CA G118D in culture, resulted in tumor growth inhibition in cell line xenograft models (PMID: 27439478). 27439478
PIK3CA mutant cervical cancer predicted - sensitive Alpelisib Case Reports/Case Series Actionable In a Phase I trial, Alpelisib (BYL719) treatment resulted in partial response in 3 patients with cervical cancer harboring PIK3CA mutations (PMID: 29401002; NCT01219699). 29401002
PIK3CA mutant head and neck squamous cell carcinoma sensitive Radiotherapy + Taselisib Preclinical - Pdx & cell culture Actionable In a preclinical study, Taselisib (GDC-0032) enhanced the effects of radiation induced apoptosis in HNSCC cell lines, cell line xenograft models, and a patient derived xenograft (PDX) model, all with PIK3CA mutations (PMID: 26589432). 26589432
PIK3CA mutant Advanced Solid Tumor sensitive A-443654 Preclinical Actionable In a preclinical study, cells expressing mutant PIK3CA demonstrated increased sensitivity to A-443654 compared to cells expressing wild-type PIK3CA (PMID: 19208828). 19208828
PIK3CA mutant lung squamous cell carcinoma no benefit Taselisib Phase I Actionable In a Phase I (SWOG S1400B) trial, Taselisib (GDC-0032) treatment did not meet primary endpoint in patients with lung squamous cell carcinoma harboring PIK3CA mutations, with only 1 responder in the primary analysis population (n=21) (PMID: 31158500; NCT02785913). 31158500
PIK3CA mutant breast cancer predicted - sensitive MLN1117 Case Reports/Case Series Actionable In a Phase I trial, MLN1117 (INK1117) treatment resulted in partial response in 3 patients with breast cancer harboring PI3CA mutations (PMID: 28490463; NCT01449370). 28490463
PIK3CA mutant Advanced Solid Tumor sensitive AZD8835 Preclinical Actionable In a preclinical study, AZD8835 inhibited growth of a variety of advanced solid tumor models with Pik3ca mutations in culture (PMID: 26839307). 26839307
PIK3CA mutant invasive bladder transitional cell carcinoma predicted - resistant Cisplatin + Gemcitabine + Sorafenib Phase II Actionable In a Phase II trial, PIK3CA mutations were more frequent in muscle-invasive urothelial bladder cancer patients that did not respond to Nexavar (sorafenib), Platinol (cisplatin) and Gemzar (gemcitabine) combination therapy than those who did respond (J Clin Oncol 35, 2017 (suppl 6S; abstract 345)). detail...
PIK3CA mutant colon cancer predicted - resistant Selumetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Koselugo (selumetinib) treatment did not induce cell death, apoptosis, or inhibit colony formation in PIK3CA mutant colon cancer cells in culture, and did not inhibit tumor growth in a cell line xenograft model (PMID: 30944457). 30944457
PIK3CA mutant breast cancer predicted - sensitive CYH33 Preclinical - Cell culture Actionable In a preclinical study, breast cancer cell lines harboring PIK3CA mutations demonstrated increased sensitivity to CYH33 compared to cell lines with wild-type PIK3CA in culture (p<0.01) (PMID: 30003928). 30003928
PIK3CA mutant liposarcoma predicted - sensitive Copanlisib Case Reports/Case Series Actionable In a Phase II trial (NCI MATCH EAY131-Z1F), Aliqopa (copanlisib) treatment resulted in a partial response in a patient with liposarcoma harboring PIK3CA mutation (J Clin Oncol 38: 2020 (suppl; abstr 3506); NCT02465060). detail...
PIK3CA mutant colorectal cancer predicted - sensitive MS417 + Pictilisib Preclinical - Cell culture Actionable In a preclinical study, Pictilisib (GDC-0941) and MS417 in combination resulted in improved growth inhibition and increased cell death compared to either agent alone in colorectal cancer cell lines harboring PIK3CA mutations in culture (PMID: 26058079). 26058079
PIK3CA mutant colon cancer predicted - resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) treatment did not induce cell death, apoptosis, or inhibit colony formation in PIK3CA mutant colon cancer cells in culture, and did not inhibit tumor growth in a cell line xenograft model (PMID: 30944457). 30944457
PIK3CA mutant colon cancer predicted - sensitive NVP-TNKS656 + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Koselugo (selumetinib) treatment in combination with NVP-TNKS656 enhanced cell death in PIK3CA mutant colon cancer cells in culture (PMID: 30944457). 30944457
PIK3CA mutant Her2-receptor positive breast cancer not predictive Ado-trastuzumab emtansine Phase III Actionable In a retrospective analysis of a Phase III trial (KATHERINE), adjuvant Kadcyla (ado-trastuzumab emtansine) treatment demonstrated similar invasive disease-free survival benefit over Herceptin (trastuzumab) in PIK3CA mutant (HR=0.54) and PIK3CA wild-type (HR=0.48) patients with Erbb2 (Her2)-positive breast cancer who had residual invasive disease after neoadjuvant therapy (J Clin Oncol 38, no. 15_suppl (May 20, 2020) 502-502; NCT01772472). detail...
PIK3CA mutant breast cancer sensitive CUDC-907 Preclinical Actionable In a preclinical study, CUDC-907 inhibited growth of human breast cancer cell lines harboring PIK3CA mutations in culture (PMID: 22693356). 22693356
PIK3CA mutant Advanced Solid Tumor sensitive Sapanisertib Preclinical Actionable In a preclinical study, human cancer cell lines harboring PIK3CA mutations were sensitive to Sapanisertib (MLN0128) as demonstrated by significant growth inhibition (PMID: 25261369). 25261369
PIK3CA mutant Advanced Solid Tumor predicted - sensitive Uprosertib Phase I Actionable In a Phase I clinical trial, GSK2141795 demonstrated safety and preliminary efficacy in patients with advanced solid tumors, with 4 patients with PIK3CA mutations and/or PTEN loss achieving stable disease for greater than 6 months (J Clin Oncol 29: 2011 (suppl; abstr 3003)). detail...
PIK3CA mutant lung non-small cell carcinoma sensitive PF-04691502 Preclinical - Cell line xenograft Actionable In a preclinical study, PF-04691502 inhibited tumor growth in non-small cell lung cancer cell line xenograft models harboring PIK3CA mutations (PMID: 21750219). 21750219
PIK3CA mutant breast cancer sensitive AZD8835 Preclinical Actionable In a preclinical study, AZD8835 inhibited tumor growth in breast cancer xenograft models harboring PIK3CA mutations (AACR; 2015. Abstract nr 2665). detail...
PIK3CA mutant Advanced Solid Tumor sensitive XL147 Preclinical Actionable In a preclinical study, tumor cell lines with PIK3CA mutations demonstrated sensitivity to XL147 in culture (PMID: 25637314). 25637314
PIK3CA mutant Advanced Solid Tumor sensitive XL147 Phase I Actionable In a Phase I clinical trial, XL147 (SAR24508) was shown to be safe and potentially efficacious, with clinical activity seen irrespective of tumor PI3K pathway molecular alterations (PMID: 24166903). 24166903
PIK3CA mutant Her2-receptor negative breast cancer no benefit Everolimus Phase III Actionable In a retrospective analysis of a Phase III trial (BOLERO-2), the presence of PIK3CA mutations did not significantly affect the efficacy of Afinitor (everolimus) in patients with hormone receptor-positive, Erbb2 (Her2)-negative breast cancer, with a HR for progression-free survival of 0.37 in PIK3CA wild-type group and a HR of 0.51 (p=0.35) in patients with PIK3CA mutations (PMID: 26503204; NCT00863655). 26503204
PIK3CA mutant endometrial cancer sensitive GDC-0980 Phase II Actionable In a Phase II trial, Apitolisib (GDC-0980) was poorly tolerated, but demonstrated efficacy in endometrial cancer patients harboring mutations in PIK3CA, PTEN, or AKT1 (J Clin Oncol 32:5s, 2014 (suppl; abstr 5513)). detail...
PIK3CA mutant Advanced Solid Tumor sensitive M2698 Preclinical Actionable In a preclinical study, MSC2363318A demonstrated anti-proliferative activity against many solid tumor cell lines with PI3K pathway genomic alterations, and inhibited tumor growth in several human cancer xenograft models of breast, pancreatic, glioblastoma and ovarian cancers (Mol Cancer Ther 2013;12(11 Suppl):A162). detail...
PIK3CA mutant Advanced Solid Tumor sensitive Alpelisib Preclinical - Cell line xenograft Actionable In a preclinical study, PIK3CA mutations were associated with sensitivity to Alpelisib (BYL719) in human tumor cell lines in culture and in xenograft models (PMID: 24608574). 24608574
PIK3CA mutant Advanced Solid Tumor sensitive Alpelisib Phase I Actionable In a Phase I trial, Alpelisib (BYL719) demonstrated safety and efficacy in patients with advanced solid tumor harboring PIK3CA mutations, resulted in a disease control rate of 58.2% (78/134, 1 complete response (CR), 7 partial response (PR), 70 stable disease (SD)), and a clinical benefit rate (CR+PR+SD>24 weeks) of 15.7% (21/134) (PMID: 29401002; NCT01219699). 29401002
PIK3CA mutant breast cancer no benefit Temsirolimus Phase II Actionable In a Phase II trial, Torisel (temsirolimus) treatment resulted in stable disease in 9.7% (3/31) of breast cancer patients positive for ER, PR or ERBB2 (HER2), however there was no association between PIK3CA mutational status and clinical benefits (PMID: 22245973). 22245973
PIK3CA mutant breast cancer no benefit GSK2126458 Phase I Actionable In a Phase I trial, GSK2126458 was well-tolerated and resulted in some efficacy in patients with breast cancer harboring a PIK3CA mutation including stable disease in 22% (2/9), however, objective response rate was not associated with PIK3CA mutations when compared to those without PIK3CA mutations (PMID: 26603258). 26603258
PIK3CA mutant breast cancer predicted - sensitive Capivasertib Preclinical Actionable In a preclinical study, AZD5363 inhibited growth in breast cancer cell lines and xenograft models expressing PIK3CA mutations (PMID: 22294718). 22294718
PIK3CA mutant breast cancer predicted - sensitive Capivasertib Phase I Actionable In a Phase I trial, treatment with AZD5363 was well-tolerated and resulted in tumor shrinkage in 46% (12/26) patients with PIK3CA-mutant breast cancer, with confirmed RECIST responses in 4% (1/28) of patients (PMID: 29066505; NCT01226316). 29066505
PIK3CA mutant endometrioid ovary carcinoma sensitive Capivasertib Phase I Actionable In a Phase I clinical trial, AZD5363 demonstrated safety and efficacy in patients with advanced solid tumors, including prolonged stable disease in one patient with a PIK3CA-mutant endometrioid ovarian cancer (American Association for Cancer Research; 06 Apr 2013-10 Apr 2013; Abstract LB-66). detail...
PIK3CA mutant Her2-receptor negative breast cancer sensitive Alpelisib Phase I Actionable In a Phase I trial, Alpelisib (BYL719) treatment resulted in a disease control rate of 60.9% (14/23, 0 complete response (CR), 1 partial response (PR), 13 stable disease (SD)), and a clinical benefit rate (CR+PR+SD>24 weeks) of 17.4% (4/23) in patients with ER-positive, ERBB2 (HER2)-negative breast cancer harboring PIK3CA mutations (PMID: 29401002; NCT01219699). 29401002
PIK3CA mutant hematologic cancer sensitive CUDC-907 Preclinical - Cell line xenograft Actionable In a preclinical study, CUDC-907 inhibited PIK3CA, blocked downstream AKT pathway activation, and induced apoptosis and cell cycle arrest in both PIK3CA wild-type and PIK3CA mutant human cancer cell lines and xenograft models of multiple solid and hematologic cancers (PMID: 22693356). 22693356
PIK3CA mutant Advanced Solid Tumor sensitive VS-5584 Preclinical Actionable In preclinical studies, VS-5584 demonstrated efficacy in a variety of cancer cell lines, particularly those harboring PIK3CA mutations (PMID: 23270925). 23270925
PIK3CA mutant head and neck squamous cell carcinoma predicted - sensitive Carboplatin + Paclitaxel + Temsirolimus Phase II Actionable In a Phase II trial, two patients with head and neck squamous cell carcinoma harboring a PIK3CA mutation who had stable disease demonstrated some tumor regression when treated with the combination of Torisel (temsirolimus), Paraplatin (carboplatin), and Taxol (paclitaxel) (PMID: 28961834). 28961834
PIK3CA mutant breast cancer sensitive CH5132799 Preclinical Actionable In a preclinical study, breast cancer cells with PIK3CA mutations, both with and without ERBB2 (HER2) amplification, demonstrated sensitivity to CH5132799 in culture (PMID: 21558396). 21558396
PIK3CA mutant Advanced Solid Tumor sensitive CUDC-907 Preclinical - Cell line xenograft Actionable In a preclinical study, CUDC-907 inhibited PIK3CA, blocked downstream AKT pathway activation, and induced apoptosis and cell cycle arrest in both PIK3CA wild-type and PIK3CA mutant human cancer cell lines and xenograft models of multiple tumor types (PMID: 22693356). 22693356
PIK3CA mutant breast cancer sensitive Sapanisertib Preclinical Actionable In a preclinical study, Sapanisertib (MLN0128) demonstrated efficacy in PIK3CA mutant breast cancer xenograft models (PMID: 23085766). 23085766
PIK3CA mutant Advanced Solid Tumor sensitive Taselisib Phase I Actionable In a Phase I trial, Taselisib (GDC-0032) demonstrated activity in patients with PIK3CA-mutant advanced solid tumors, in the absence of alterations in the MAPK or PTEN pathways (Cancer Res October 1, 2014 74:915). detail...
PIK3CA mutant ovarian cancer sensitive OSI-027 Preclinical - Cell line xenograft Actionable In a preclinical study, OSI-027 inhibited tumor growth in ovarian cancer cell line xenograft models harboring PIK3CA mutations (PMID: 21673091). 21673091
PIK3CA mutant female reproductive organ cancer predicted - sensitive Capivasertib Phase I Actionable In a Phase I trial, treatment with AZD5363 was well-tolerated and resulted in tumor shrinkage in 56% (14/25) patients with PIK3CA-mutant gynecological cancers, however, the response rate was modest with confirmed RECIST responses in 8% (2/26) of patients (PMID: 29066505; NCT01226316). 29066505
PIK3CA mutant stomach cancer sensitive BAY1082439 Preclinical Actionable In a preclinical study, BAY1082439 inhibited growth of gastric cancer cells harboring PIK3CA mutations in culture and xenograft models (AACR; 2015. Abstract nr 2674). detail...
PIK3CA mutant ovarian cancer sensitive Buparlisib + Olaparib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Buparlisib (BKM120) and Lynparza (olaparib) worked synergistically to induce apoptosis and inhibit growth of ovarian cancer cell lines harboring PIK3CA mutations in culture, and induced apoptosis and decreased proliferation of PIK3CA-mutant ovarian cancer cell line xenograft models (PMID: 26909613). 26909613
PIK3CA mutant endometrial cancer no benefit Temsirolimus Phase II Actionable In a retrospective study of a Phase II trial, mutation status of PIK3CA was not associated with progression-free survival or response rate in advanced endometrial cancer patients treated with Torisel (temsirolimus) (PMID: 27016228). 27016228
PIK3CA mutant breast cancer sensitive Alpelisib + GSK2334470 Preclinical - Cell line xenograft Actionable In a preclinical study, GSK2334470 resensitized Alpelisib (BYL719)-resistant breast cancer cell lines harboring PIK3CA mutations to Alpelisib (BYL719) in culture and in cell line xenograft models (PMID: 27451907). 27451907
PIK3CA mutant colon cancer sensitive Dactolisib Preclinical Actionable In a preclinical study, BEZ235 demonstrated efficacy in promoting apoptosis of colon cancer cells harboring a PIK3CA mutation in culture (PMID: 22543857). 22543857
PIK3CA mutant hepatocellular carcinoma decreased response Sorafenib Clinical Study - Cohort Actionable In a clinical case study, Nexavar (sorafenib) treatment of patients with hepatocellular carcinoma harboring Mtor pathway mutations in PIK3CA, PTEN, TSC2, or TSC1 (n=12), resulted in a lower disease control rate (8.3% vs. 40.2%), shorter progression-free survival (1.9 months vs. 5.3 months) and shorter overall survival (10.4 months vs. 17.9 months) compared to patients without mutations in this pathway (n=67) (PMID: 30373752; NCT01775072). 30373752
PIK3CA mutant lung non-small cell carcinoma predicted - sensitive Sulindac Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cell lines harboring either a PIK3CA mutation or PIK3CA amplification demonstrated increased sensitivity to Clinoril (sulindac) compared to cell lines with wild-type PIK3CA, resulting in decreased proliferation in culture (PMID: 30683736). 30683736
PIK3CA mutant lung non-small cell carcinoma sensitive PWT33597 Preclinical Actionable In a preclinical study, PWT33597 decreased signaling of mTOR and PIK3 pathways in non-small cell lung cancer cells with Pik3ca mutations (Cancer Res 2011;71(8 Suppl):Abstract nr 4485). detail...
PIK3CA mutant squamous cell carcinoma sensitive Carboxyamidotriazole Orotate Phase I Actionable In a Phase I clinical trial, carboxyamidotriazole orotate treatment demonstrated some efficacy in patients with various solid tumors including squamous cell carcinomas (tonsil) with PI3KCA and NRAS mutations (J Clin Oncol 31, 2013 (suppl; abstr 2518)). detail...
PIK3CA mutant lung squamous cell carcinoma no benefit Capivasertib Case Reports/Case Series Actionable In a Phase II trial (NLMT), Capivasertib (AZD5363) treatment did not result in a conformed response (0/4) or durable clinical benefit (0/4) in patients with squamous cell lung cancer harboring PIK3CA mutations, thus the cohort was closed due to futility (PMID: 32669708, NCT02664935). 32669708
PIK3CA mutant estrogen-receptor positive breast cancer predicted - sensitive Letrozole Phase III Actionable In a Phase III trial, estrogen-receptor positive breast cancer patients harboring a PIK3CA mutation demonstrated a greater benefit when treated with Femara (letrozole) compared to Nolvadex (tamoxifen) (PMID: 29902286; NCT00004205). 29902286
PIK3CA mutant Her2-receptor negative breast cancer no benefit Capivasertib + Paclitaxel Phase II Actionable In a Phase II trial, the addition of AZD5363 to Taxol (paclitaxel) therapy did not improve progression-free survival compared to placebo (10.9 vs 10.8 months) in patients with PIK3CA-mutant, Esr1-positive, Erbb2 (Her2)-negative breast cancer (PMID: 30860570; NCT01625286). 30860570
PIK3CA mutant colon cancer predicted - resistant Pimasertib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) treatment did not induce cell death, apoptosis, or inhibit colony formation in PIK3CA mutant colon cancer cells in culture (PMID: 30944457). 30944457
PIK3CA mutant Advanced Solid Tumor predicted - sensitive Copanlisib Phase II Actionable In a Phase II trial (NCI MATCH EAY131-Z1F), Aliqopa (copanlisib) treatment resulted in an objective response rate of 11% (3/28, 3 partial response) and a clinical benefit rate of 32% (9/28) in patients with advanced solid tumors harboring PIK3CA mutations (J Clin Oncol 38: 2020 (suppl; abstr 3506); NCT02465060). detail...
PIK3CA mutant Advanced Solid Tumor sensitive Onatasertib Phase I Actionable In a Phase I trial, CC-223 demonstrated safety and preliminary efficacy in patients with solid tumors, including stable disease for greater than 110 days in 2 patients with PIK3CA mutation or PTEN deletion (PMID: 26177599). 26177599 detail...
PIK3CA mutant Advanced Solid Tumor sensitive PX-866 Phase I Actionable In a Phase I trial, PX-866 demonstrated efficacy and was well tolerated in patients with advanced solid tumor with both PIK3CA wild-type and mutant status (PMID: 22693357). 22693357
PIK3CA mutant colon cancer predicted - sensitive NVP-TNKS656 + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, Mekinist (trametinib) treatment in combination with NVP-TNKS656 enhanced cell death in PIK3CA mutant colon cancer cells in culture, and induced apoptosis and inhibited tumor growth in a cell line xenograft model (PMID: 30944457). 30944457
PIK3CA mutant cervical cancer not predictive Perifosine Phase II Actionable In a Phase II trial , Perifosine (KRX-0401) treatment was well-tolerated, resulted in stable disease as best response in patients with recurrent cervical cancer, no significant difference in disease control rate (11.1%, 2/18 vs 25%, 2/8, p=0.56), median progression-free survival (HR=1.06, p=0.81), or median overall survival (HR=1.66, p=0.26) was identified between PIK3CA wild-type and PIK3CA mutant patients (PMID: 28864978). 28864978
PIK3CA mutant endometrial cancer no benefit MK2206 Phase II Actionable In a Phase II trial, MK2226 demonstrated limited benefit in endometrial cancer patients regardless of PIK3CA status, with partial responses in 6% (2/37) of patients, 19% (7/37; 5 with serous histology) remaining progression-free for at least 6 mo, and a median progression-free survival (PFS) of 2.0 mo in the overall population, and partial responses in 11% (11/9), 33% (3/9) progression-free for 6 mo, and a median PFS of 1.7 mo in the group of patients with PIK3CA mutations (PMID: 31714586; NCT01307631). 31714586
PIK3CA mutant triple-receptor negative breast cancer sensitive Pictilisib Preclinical - Cell culture Actionable In a preclinical study, triple-receptor negative breast cancer cell lines harboring PIK3CA mutations demonstrated increased sensitivity to Pictilisib (GDC-0941) in culture (PMID: 27196766). 27196766
PIK3CA mutant cervical cancer decreased response Cetuximab Phase II Actionable In a Phase II clinical trial, Erbitux (cetuximab) treatment, in addition to radiochemotherapy, did not result in any complete responses (0/8) and demonstrated a worse disease free survival when compared to radiochemotherapy alone in cervical cancer patients harboring PIK3CA mutations (PMID: 25724520). 25724520
PIK3CA mutant Advanced Solid Tumor sensitive BAY1082439 Preclinical Actionable In a preclinical study, BAY1082439 induced regression in xenograft models of advanced solid tumors with PIK3CA mutations (Cancer Res April 15, 2012 72; 2799). detail...
PIK3CA mutant colorectal cancer sensitive Alpelisib Phase I Actionable In a Phase I trial, Alpelisib (BYL719) treatment resulted in a disease control rate of 34.3% (12/35, 0 complete response (CR), 2 partial response (PR), 10 stable disease (SD)), and a clinical benefit rate (CR+PR+SD>24 weeks) of 8.6% (3/35) in patients with colorectal cancer harboring PIK3CA mutations (PMID: 29401002; NCT01219699). 29401002
PIK3CA mutant gastric adenocarcinoma sensitive Fluorouracil + PI-103 Preclinical Actionable In a preclinical study, PI-103 enhanced sensitivity to 5-FU in gastric cancer cells with mutant PIK3CA (PMID: 22336586). 22336586
PIK3CA mutant clear cell adenocarcinoma predicted - sensitive Copanlisib Case Reports/Case Series Actionable In a Phase II trial (NCI MATCH EAY131-Z1F), Aliqopa (copanlisib) treatment resulted in a partial response in a patient with clear cell carcinoma of anterior abdominal wall harboring PIK3CA mutation (J Clin Oncol 38: 2020 (suppl; abstr 3506); NCT02465060). detail...
PIK3CA mutant Advanced Solid Tumor sensitive AT-7867 Preclinical Actionable In a preclinical study, AT-7867 inhibited proliferation in several human tumor cell lines harboring PIK3CA mutations in culture (PMID: 20423992). 20423992
PIK3CA mutant colon cancer predicted - resistant NVP-TNKS656 Preclinical - Cell line xenograft Actionable In a preclinical study, NVP-TNKS656 treatment alone did not significantly inhibit viability of PIK3CA mutant colon cancer cells in culture, and did not inhibit tumor growth in a cell line xenograft model (PMID: 30944457). 30944457
PIK3CA mutant estrogen-receptor positive breast cancer no benefit Fulvestrant + Pictilisib Phase II Actionable In a Phase II trial, Falsodex (fulvestrant) and Pictilisib (GDC-0941) combination treatment resulted in similar progression free survival in ER positive breast cancer patients harboring PIK3CA mutations and those who were PIK3CA wild-type (PMID: 27174596). 27174596
PIK3CA mutant ovarian cancer not predictive Perifosine Phase II Actionable In a Phase II trial , Perifosine (KRX-0401) treatment was well-tolerated, resulted in stable disease as best response in patients with recurrent ovarian cancer, no significant difference in disease control rate (12.5%, 2/16 vs 40%, 2/5, p=0.22), median progression-free survival (HR=0.57, p=0.32), or median overall survival (HR=1.37, p=0.58) was identified between PIK3CA wild-type and PIK3CA mutant patients (PMID: 28864978). 28864978
PIK3CA mutant head and neck cancer sensitive Alpelisib Phase I Actionable In a Phase I trial, Alpelisib (BYL719) treatment resulted in a disease control rate of 68.4% (13/19, 0 complete response (CR), 0 partial response (PR), 13 stable disease (SD)), and a clinical benefit rate (CR+PR+SD>24 weeks) of 10.5% (2/19) in patients with head and neck cancer harboring PIK3CA mutations (PMID: 29401002; NCT01219699). 29401002
PIK3CA mutant endometrial cancer sensitive CH5132799 Preclinical Actionable In a preclinical study, CH5132799 inhibited proliferation of endometrial cancer cells with PIK3CA mutations in culture (PMID: 21558396). 21558396
PIK3CA mutant lung adenocarcinoma no benefit Capivasertib Case Reports/Case Series Actionable In a Phase II trial (NLMT), Capivasertib (AZD5363) treatment did not result in a conformed response (0/8) or durable clinical benefit (0/8) in patients with lung adenocarcinoma harboring mutations in PIK3CA, PTEN, or AKT, thus the cohort was closed due to futility (PMID: 32669708, NCT02664935). 32669708
PIK3CA mutant endometrial carcinoma no benefit Copanlisib Phase II Actionable In a Phase II (NRG-GY008) trial, Aliqopa (copanlisib) was well tolerated but demonstrated limited efficacy, resulted in stable disease as best response in 54.5% (6/11) of patients with endometrial carcinoma harboring PIK3CA mutations, with a median progression-free survival of 2.8 months and a median overall survival of 15.2 months (PMID: 31934607). 31934607
PIK3CA mutant breast cancer sensitive Pictilisib Preclinical Actionable In a preclinical study, GDC-0941 inhibited growth and induced apoptosis in breast cancer cells expressing PIK3CA mutations (PMID: 24601221). 24601221
PIK3CA mutant breast cancer sensitive Letrozole + Taselisib Phase Ib/II Actionable In a Phase Ib trial, Taselisib (GDC-0032) and Femara (letrozole) combination therapy resulted in an overall response rate of 38% in breast cancer patients with PIK3CA mutations, compared to 9% in patients with wild-type PIK3CA (Cancer Res May 1, 2015 75; PD5-2). detail...
PIK3CA mutant breast cancer no benefit MK2206 Phase II Actionable In a Phase II trial, MK2206 demonstrated limited clinical efficacy in patients with advanced breast cancer harboring mutations in PIK3CA (n=14) or AKT1 (n=4), resulted in an objective response rate of 5.6% (1/18, 1 partial response) and a 6-month progression-free survival rate of 5.6%, with no significant target inhibition in tumor biopsies (PMID: 31277699; NCT01277757). 31277699
PIK3CA mutant breast cancer sensitive OSI-027 Preclinical - Cell line xenograft Actionable In a preclinical study, OSI-027 induced tumor regression in breast cancer cell line xenograft models harboring PIK3CA mutations (PMID: 21673091). 21673091
PIK3CA mutant Advanced Solid Tumor sensitive Carboxyamidotriazole Orotate Phase I Actionable In a Phase I clinical trial, carboxyamidotriazole orotate treatment demonstrated some efficacy in patients with various solid tumors, including patients harboring PIK3CA mutations (J Clin Oncol 31, 2013 (suppl; abstr 2518)). detail...
PIK3CA mutant stomach cancer predicted - sensitive MLN1117 Case Reports/Case Series Actionable In a Phase I trial, MLN1117 (INK1117) treatment resulted in a partial response in one patient with gastric cancer harboring a PIK3CA mutation (PMID: 28490463; NCT01449370). 28490463
PIK3CA mutant uterine cancer predicted - sensitive Copanlisib Case Reports/Case Series Actionable In a Phase II trial (NCI MATCH EAY131-Z1F), Aliqopa (copanlisib) treatment resulted in a partial response in a patient with uterine cancer harboring PIK3CA mutation (J Clin Oncol 38: 2020 (suppl; abstr 3506); NCT02465060). detail...
PIK3CA mutant breast cancer sensitive AT13148 Preclinical - Cell line xenograft Actionable In a preclinical study, a ERBB3 (HER3) positive breast cancer cell line xenograft model harboring a PIK3CA mutation was demonstrated decreased tumor growth when treated with AT13148 (PMID: 22781553). 22781553
PIK3CA mutant colon cancer sensitive PWT33597 Preclinical Actionable In a preclinical study, PWT33597 decreased signaling of mTOR and PIK3 pathways in colon cancer cells with Pik3ca mutations (Cancer Res 2011;71(8 Suppl):Abstract nr 4485). detail...
PIK3CA mutant Advanced Solid Tumor no benefit Alpelisib + Infigratinib Phase Ib/II Actionable In a Phase Ib trial, treatment with the combination of Piqray (alpelisib) and Infigratinib (BGJ398) resulted in partial response (PR) in 9.7% (6/62) and disease control (PR or stable disease) in 61.3% (34/62) of patients with advanced solid tumors harboring a PIK3CA mutation with or without an FGFR alteration, however, the efficacy was not deemed great enough to pursue further development (JCO Precision Oncology 2019 :3, 1-13). detail...
PIK3CA mutant Advanced Solid Tumor sensitive Bevacizumab + Pegylated liposomal-doxorubicin + Temsirolimus Clinical Study Actionable In a clinical study, the combination of Torisel (temsirolimus) plus Avastin (bevacizumab) and Doxil (pegylated liposomal-doxorubicin) resulted in a partial response in patients with advanced solid tumors harboring PIK3CA mutations (PMID: 21216929). 21216929
PIK3CA mutant Advanced Solid Tumor sensitive Bevacizumab + Pegylated liposomal-doxorubicin + Temsirolimus Clinical Study Actionable In a clinical study, the combination of Torisel (temisirolimus) plus Avastin (bevacizumab) and Doxil (pegylated liposomal-doxirubicin) resulted in stable disease in patients with advanced solid tumors harboring PIK3CA mutations (PMID: 21216929). 21216929
PIK3CA mutant breast cancer predicted - sensitive GDC-0077 Preclinical - Pdx & cell culture Actionable In a preclinical study, GDC-0077 inhibited proliferation and induced apoptosis in PIK3CA-mutant breast cancer cell lines in culture, and induced apoptosis and tumor regression in PIK3CA-mutant breast cancer cell line and patient-derived xenograft models (AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 156). detail...
PIK3CA mutant prostate cancer sensitive CH5132799 Preclinical Actionable In a preclinical study, CH5132799 inhibited proliferation of prostate cancer cells with PIK3CA mutations in culture (PMID: 21558396). 21558396
PIK3CA mutant breast cancer sensitive VS-5584 Preclinical Actionable In a preclinical study, PIK3CA mutant breast cancer cells showed increased sensitivity to VS-5584 compared to PIK3CA wild-type cells in culture (PMID: 23270925). 23270925
PIK3CA mutant breast adenocarcinoma sensitive Acalisib Preclinical - Cell line xenograft Actionable In a preclinical study, Acalisib (GS-9820) resulted in tumor growth inhibition in xenograft models of breast adenocarcinoma harboring a PIK3CA mutation (Mol Cancer Ther 2009;8(12 Suppl):B136). detail...
PIK3CA mutant endometrial cancer sensitive Pictilisib Preclinical Actionable In a preclinical study, endometrioid endometrial cancer cell lines harboring PIK3CA mutations demonstrated increased sensitivity to GDC-0941 (Pictilisib) induced growth inhibition comparing to PIK3CA wild-type cells in culture (PMID: 23674493). 23674493
PIK3CA mutant colon cancer predicted - resistant Refametinib Preclinical - Cell culture Actionable In a preclinical study, Refametinib (BAY86-9766) treatment did not induce cell death, apoptosis, or inhibit colony formation in PIK3CA mutant colon cancer cells in culture (PMID: 30944457). 30944457
PIK3CA mutant ovarian cancer sensitive Temsirolimus Phase I Actionable In a Phase I clinical trial, Torisel (temsirolimus) demonstrated limited efficacy in ovarian cancer patients with PIK3CA mutations (PMID: 22271473). 22271473
PIK3CA mutant ovarian cancer sensitive Temsirolimus Case Reports/Case Series Actionable In a clinical study, an ovarian cancer patient harboring a PIK3CA E542 mutation demonstrated stable disease when treated with Torisel (temsirolimus) (PMID: 21216929). 21216929
PIK3CA mutant estrogen-receptor positive breast cancer sensitive AZD8835 Preclinical Actionable In a preclinical study, AZD8835 inhibited proliferation of estrogen receptor (ER)-positive breast cancer cells harboring PIK3CA mutations in culture and suppressed tumor growth in xenograft models (PMID: 26839307). 26839307
PIK3CA mutant endometrial cancer sensitive Alpelisib Case Reports/Case Series Actionable In a Phase I trial, Alpelisib (BYL719) treatment resulted in 1 complete response and 1 partial response in patients with endometrial cancer harboring PIK3CA mutations (PMID: 29401002; NCT01219699). 29401002
PIK3CA mutant ovarian cancer sensitive CH5132799 Preclinical Actionable In a preclinical study, CH5132799 inhibited proliferation of ovarian cancer cells with PIK3CA mutations in culture (PMID: 21558396). 21558396
PIK3CA mutant triple-receptor negative breast cancer predicted - sensitive Ipatasertib + Paclitaxel Phase II Actionable In a Phase II trial, Ipatasertib (GDC-0068) in combination with Abraxane (paclitaxel) resulted in improved progression free survival (6.2 vs 4.9 months) compared to placebo in triple-receptor negative breast cancer patients harboring mutations in PIK3CA, AKT1, or PTEN (J Clin Oncol 35, 2017 (suppl; abstr 1009)). detail...
PIK3CA mutant triple-receptor negative breast cancer sensitive Palbociclib + Pictilisib Preclinical Actionable In a preclinical study, Ibrance (palbociclib) and Pictilisib (GDC-0941) worked synergistically to inhibit the survival of triple-receptor negative breast cancer cell lines harboring PIK3CA mutations in culture (PMID: 27020857). 27020857
PIK3CA mutant Advanced Solid Tumor sensitive GDC-0980 Phase I Actionable In a Phase I trial, Apitolisib (GDC-0980) treatment resulted in partial response in 21% (3/14) and stable disease in 57% (8/14) of patients with advanced solid tumors harboring PIK3CA mutations (PMID: 26787751). 26787751
PIK3CA mutant stomach cancer sensitive Dactolisib Preclinical Actionable In a preclinical study, BEZ235 demonstrated efficacy in promoting apoptosis of gastric cancer cells harboring a PIK3CA mutation in culture (PMID: 22543857). 22543857
PIK3CA mutant estrogen-receptor positive breast cancer no benefit Fulvestrant Phase II Actionable In a Phase II trial, Falsodex (fulvestrant) treatment resulted in similar progression free survival in ER positive breast cancer patients harboring PIK3CA mutations and those who were PIK3CA wild-type (PMID: 27174596). 27174596
PIK3CA mutant endometrial cancer not predictive Perifosine Phase II Actionable In a Phase II trial , Perifosine (KRX-0401) treatment was well-tolerated, resulted in stable disease as best response in patients with recurrent endometrial cancer, no significant difference in disease control rate (47.1%, 8/17 vs 14.3%, 1/7, p=0.19), median progression-free survival (HR=1.71, p=0.30), or median overall survival (HR=0.92, p=0.88) was identified between PIK3CA wild-type and PIK3CA mutant patients (PMID: 28864978). 28864978
PIK3CA mutant Advanced Solid Tumor sensitive MLN1117 Preclinical Actionable In a preclinical study, MLN1117 inhibited proliferation of tumor cells harboring oncogenic PIK3CA mutations in culture and inhibited tumor growth in PIK3CA mutant xenograft models (Cancer Ther 2011;10(11 Suppl):Abstract nr A171). detail...
PIK3CA mutant Advanced Solid Tumor sensitive MLN1117 Phase I Actionable In a Phase I trial, MLN1117 demonstrated safety and preliminary efficacy in a variety of patients with advanced solid tumors carrying PIK3CA mutations (Journal of Clinical Oncology, 2015 ASCO Annual Meeting Vol 33, No 15_suppl., 2015: 2501). detail...
PIK3CA mutant Her2-receptor positive breast cancer sensitive CCT128930 Preclinical - Cell line xenograft Actionable In a preclinical study, CCT128930 induced growth arrest and inhibited tumor growth in a xenograft model of a ERBB2 (HER2)-positive human breast cancer cell line harboring a PIK3CA mutation (PMID: 21191045). 21191045
CDKN2A mut PIK3CA mut breast cancer sensitive Sapanisertib Preclinical Actionable In a preclinical study, a breast cancer cell line harboring mutations in PIK3CA and CDKN2A demonstrated sensitivity to Sapanisertib (MLN0128) in culture (PMID: 25261369). 25261369
ERBB2 amp PIK3CA mut breast cancer sensitive CUDC-907 Preclinical Actionable In a preclinical study, CUDC-907 inhibited downstream signaling and growth of PIK3CA-mutant breast cancer cells with ERBB2 amplification in culture (PMID: 22693356). 22693356
ERBB2 amp PIK3CA mut Her2-receptor positive breast cancer sensitive Ipatasertib Preclinical - Cell line xenograft Actionable In a preclinical study, ERBB2 (HER2)-receptor positive breast cancer cell line xenograft models harboring amplification of ERBB2 (HER2) and a PIK3CA mutation demonstrated sensitivity to treatment with Ipatasertib (GDC-0068), resulting in inhibition of tumor growth (PMID: 24141624). 24141624
ERBB2 amp PIK3CA mut Her2-receptor positive breast cancer sensitive Copanlisib Preclinical - Cell line xenograft Actionable In a preclinical study, Aliqopa (copanlisib) promoted tumor regression in xenograft models of a human ERBB2 (HER2)-amplified breast cancer cell line harboring a PIK3CA activating mutation (PMID: 24170767). 24170767
ERBB2 amp PIK3CA mut uterine corpus serous adenocarcinoma sensitive Neratinib + Taselisib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Nerlynx (neratinib) and Taselisib (GDC-0032), compared to either agent alone, resulted in greater inhibition of cell cycle activity in a uterine serous carcinoma cell line harboring ERBB2 (HER2) amplification and a PIK3CA mutation in culture, and in xenograft models, showed increased tumor growth inhibition and tumor regression (PMID: 26333383). 26333383
ERBB2 pos PIK3CA mut Her2-receptor positive breast cancer decreased response Lapatinib Clinical Study - Cohort Actionable In a clinical study, a retrospective analysis of Tykerb (lapatinib) treatment in ERBB2 (HER2) positive breast cancer patients demonstrated patients harboring a PIK3CA mutation trended towards a decreased response when compared to patients with wild-type PIK3CA (PMID: 28177460). 28177460
ERBB2 pos PIK3CA mut Her2-receptor positive breast cancer decreased response Capecitabine + Lapatinib Phase III Actionable In a Phase III trial, Tykerb (lapatinib) and Xeloda (capecitabine) combination treatment resulted in decreased median progression free survival (4.3 vs. 6.4 months), median overall survival (17.3 vs. 27.8 months), and overall response rate(17.1% vs. 39.7%) in ERBB2 (HER2) positive breast cancer patients harboring PIK3CA mutations compared to PIK3CA wild type patients (PMID: 26920887). 26920887
ERBB2 pos PIK3CA mut Her2-receptor positive breast cancer predicted - sensitive Neratinib Phase III Actionable In a Phase III trial (ExteNET), Nerlynx (neratinib) treatment resulted in improved 5-year invasive disease-free survival (92.4% vs 84.5%, HR=0.41, p=0.028) and clinical benefit (HR=0.40, p=0.041) compared to placebo in patients with ERBB2 (HER2)-positive early breast cancer who completed trastuzumab-based adjuvant therapy, and harbored PIK3CA amplification (n=61) or mutations (n=210), including H1047R (n=110), E542K (n=18), and E545K/D (n=82) (PMID: 30867034; NCT00878709). 30867034
ERBB2 pos PIK3CA mut Her2-receptor positive breast cancer decreased response Trastuzumab Clinical Study - Cohort Actionable In a clinical study, a retrospective analysis of Herceptin (trastuzumab) treatment in ERBB2 (HER2) positive breast cancer patients demonstrated patients harboring a PIK3CA mutation trended towards a decreased response when compared to patients with wild-type PIK3CA (PMID: 28177460). 28177460
ERBB2 pos PIK3CA mut Her2-receptor positive breast cancer decreased response Lapatinib + Trastuzumab Clinical Study - Cohort Actionable In a clinical study, a retrospective analysis of the combined treatment, Herceptin (trastuzumab) and Tykerb (lapatinib), in ERBB2 (HER2) positive breast cancer patients demonstrated patients harboring a PIK3CA mutation trended towards a decreased response when compared to patients with wild-type PIK3CA (PMID: 28177460). 28177460
ERBB2 pos PIK3CA mut Her2-receptor positive breast cancer decreased response Lapatinib + Trastuzumab Phase II Actionable In a Phase II trial, ERBB2-positive breast cancer patients harboring PIK3CA mutations demonstrated lower pathologic complete remission rate (12.5%) compared to those with wild-type PIK3CA (48.4%) after Herceptin (trastuzumab) and Tykerb (lapatinib) combination therapy (PMID: 26245675). 26245675
ERBB2 pos PIK3CA mut Her2-receptor positive breast cancer sensitive AT13148 Preclinical - Cell line xenograft Actionable In a preclinical study, AT13148 inhibited tumor growth in a ERBB2 (HER2)-positive human breast cancer cell line xenograft model harboring mutant PIK3CA (PMID: 22781553). 22781553
ERBB2 over exp PIK3CA mut breast cancer sensitive Miransertib + Paclitaxel Preclinical - Cell line xenograft Actionable In a preclinical study, a breast cancer xenograft model with ERBB2 (HER2) over expression and harboring a PIK3CA mutation was sensitive to the combination treatment of Miransertib (ARQ092) and Taxol (paclitaxel), demonstrating greater inhibition of tumor growth when compared to treatment with either agent alone (PMID: 26469692). 26469692
ERBB2 over exp PIK3CA mut Her2-receptor positive breast cancer sensitive PKI-179 Preclinical - Cell line xenograft Actionable In a preclinical study, PKI-179 inhibited growth of breast cancer cells harboring PIK3CA mutations and ERBB2 (HER2) over expression in culture and cell line xenograft models (PMID: 20797855). 20797855
ERBB2 over exp PIK3CA mut breast cancer sensitive Miransertib + Trastuzumab Preclinical - Cell line xenograft Actionable In a preclinical study, a breast cancer xenograft model with ERBB2 (HER2) over expression and harboring a PIK3CA mutation was sensitive to the combination treatment of Miransertib (ARQ092) and Herceptin (trastuzumab), demonstrating greater inhibition of tumor growth when compared to treatment with either agent alone (PMID: 26469692). 26469692
FGFR1 over exp PIK3CA mut estrogen-receptor positive breast cancer sensitive Alpelisib + Lucitanib Preclinical - Cell culture Actionable In a preclinical study, an estrogen-receptor positive breast cancer cell line over expressing FGFR1 and expressing a PIK3CA mutation demonstrated sensitivity to the combination of Alpelisib (BYL719) and Lucitanib (E-3810) in culture (PMID: 27126994). 27126994
BRAF V600E PIK3CA mut colorectal cancer sensitive ASN003 Preclinical - Cell line xenograft Actionable In a preclinical study, a colorectal cancer cell line xenograft model co-harboring BRAF V600E and a PIK3CA mutation demonstrated tumor growth inhibition when treated with ASN003 (Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B100). detail...
ERBB2 mut PIK3CA mut breast cancer predicted - resistant Neratinib Case Reports/Case Series Actionable In a Phase II trial (SUMMIT), 6 of 7 patients with ERBB2 (HER2)-mutant breast cancer who progressed on Nerlynx (neratinib) harbored either a PIK3CA (n=5) or PIK3R1 (n=1) mutation (PMID: 31978326). 31978326
AKT1 mut PIK3CA mut Her2-receptor negative breast cancer sensitive Capivasertib Preclinical - Pdx Actionable In a preclinical study, PIK3CA and AKT1 mutations are associated with increased sensitivity to Capivasertib (AZD5363) treatment in patient-derived xenograft (PDX) models of Her2-negative breast cancer compared to PDX models harboring AKT1, PIK3CA, and PTEN mutations (PMID: 32220884). 32220884
CTNNB1 S33Y PIK3CA mut colon cancer resistant NVP-TNKS656 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, PIK3CA mutant colon cancer cells expressing CTNNB1 S33Y demonstrated suppression of cell death following Mekinist (trametinib) and NVP-TNKS656 combination treatment in culture (PMID: 30944457). 30944457
CTNNB1 mut PIK3CA mut colon cancer predicted - resistant NVP-TNKS656 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) treatment in combination with NVP-TNKS656 did not induce cell death in PIK3CA and CTNNB1 mutant colon cancer cells in culture (PMID: 30944457). 30944457
CTNNB1 mut PIK3CA mut colon cancer predicted - resistant NVP-TNKS656 Preclinical - Cell culture Actionable In a preclinical study, NVP-TNKS656 treatment did not induce cell death in PIK3CA and CTNNB1 mutant colon cancer cells in culture (PMID: 30944457). 30944457
CTNNB1 wild-type PIK3CA mut colon cancer predicted - sensitive NVP-TNKS656 Preclinical - Cell culture Actionable In a preclinical study, NVP-TNKS656 treatment induced cell death in colon cancer cells with wild-type CTNNB1 and mutant PIK3CA in culture (PMID: 30944457). 30944457
CTNNB1 wild-type PIK3CA mut colon cancer predicted - sensitive NVP-TNKS656 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) treatment in combination with NVP-TNKS656 induced cell death in colon cancer cells with wild-type CTNNB1 and mutant PIK3CA in culture (PMID: 30944457). 30944457
PIK3CA H1047X colorectal cancer predicted - resistant Bevacizumab + Temsirolimus Case Reports/Case Series Actionable In a clinical study, a colorectal cancer patient harboring a mutation at PIK3CA H1047 demonstrated progressive disease when treated with Torisel (temsirolimus) and Avastin (bevacizumab) (PMID: 21216929). 21216929
PIK3CA H1047X lung non-small cell carcinoma sensitive Taselisib Phase I Actionable In a Phase I trial, a non-small cell lung carcinoma patient harboring a mutation at PIK3CA H1047 demonstrated a confirmed partial response when treated with Taselisib (GDC-0032) (PMID: 28331003). 28331003
PIK3CA H1047X small intestine adenocarcinoma predicted - resistant Bortezomib + Temsirolimus + Topotecan Case Reports/Case Series Actionable In a clinical study, the combination of Torisel (temsirolimus) plus Velcade (bortezomib) and Hycamtin (topotecan) resulted in progressive disease in a patient with small intestine adenocarcinoma harboring a PIK3CA H1047 mutation (PMID: 21216929). 21216929
PIK3CA H1047X endometrial mixed adenocarcinoma no benefit Copanlisib Case Reports/Case Series Actionable In a Phase II (NRG-GY008) trial, Aliqopa (copanlisib) was well tolerated but demonstrated limited efficacy, resulted in progressive disease in a patient with endometrial mixed adenocarcinoma harboring a PIK3CA H1047 mutation (PMID: 31934607). 31934607
PIK3CA H1047X endometrial adenocarcinoma no benefit Copanlisib Case Reports/Case Series Actionable In a Phase II (NRG-GY008) trial, Aliqopa (copanlisib) was well tolerated but demonstrated limited efficacy, resulted in progressive disease in a patient with endometrioid adenocarcinoma harboring a PIK3CA H1047 mutation (PMID: 31934607). 31934607
PIK3CA H1047X endometrial adenocarcinoma predicted - sensitive Temsirolimus Case Reports/Case Series Actionable In a clinical study, a patient with endometrial adenocarcinoma harboring a PIK3CA H1047 mutation demonstrated a partial response when treated with Torisel (temsirolimus) (PMID: 21216929). 21216929
BRAF V600X PIK3CA H1047X ovarian carcinoma predicted - sensitive Bevacizumab + Pegylated liposomal-doxorubicin + Temsirolimus Case Reports/Case Series Actionable In a clinical study, the combination of Torisel (temsirolimus) plus Avastin (bevacizumab) and Doxil (pegylated liposomal-doxorubicin) resulted in a partial response in a patient with ovarian clear cell carcinoma harboring PIK3CA H1047 and BRAF V600 mutations (PMID: 21216929). 21216929
ERBB2 amp PIK3CA H1047X Her2-receptor positive breast cancer decreased response Poziotinib Phase II Actionable In a Phase II trial, the presence of PIK3CA activating mutations including E542X, E545X, and H1047X correlated with shorter progression-free survival (2.66 months) compared to PIK3CA wild-type or other mutations (4.24 month, HR=1.68, p=0.033) in patients with metastatic Erbb2 (Her2)-positive (amplification or overexpression) breast cancer treated with Poziotinib (HM781-36B) (PMID: 30720867, NCT02418689). 30720867
ERBB2 over exp PIK3CA H1047X Her2-receptor positive breast cancer decreased response Poziotinib Phase II Actionable In a Phase II trial, the presence of PIK3CA activating mutations including E542X, E545X, and H1047X correlated with shorter progression-free survival (2.66 months) compared to PIK3CA wild-type or other mutations (4.24 month, HR=1.68, p=0.033) in patients with metastatic Erbb2 (Her2)-positive (amplification or overexpression) breast cancer treated with Poziotinib (HM781-36B) (PMID: 30720867, NCT02418689). 30720867
PIK3CA E78K PIK3CA E726K PIK3CA D939G estrogen-receptor positive breast cancer no benefit Alpelisib + Letrozole Phase Ib/II Actionable In a Phase Ib trial, an estrogen-receptor positive breast cancer patient harboring PIK3CA mutations, E78K, D939G, and E726K, demonstrated progressive disease when treated with a combination of Femara (letrozole) and Alpelisib (BYL719) (PMID: 27126994). 27126994
PIK3CA Q546R prostate cancer sensitive CH5132799 Preclinical Actionable In a preclinical study, CH5132799 inhibited proliferation of prostate cancer cells harboring PIK3CA Q546R in culture (PMID: 21558396). 21558396
PIK3CA V344G glioblastoma multiforme no benefit YM-024 Preclinical Actionable In a preclinical study, YM-024 did not inhibit proliferation of glioblastoma cell lines harboring PIK3CA V344G in culture (PMID: 24718026). 24718026
PIK3CA V952A colorectal cancer resistant Cetuximab + Fluorouracil Case Reports/Case Series Actionable In a clinical study, PIK3CA V952A was identified as a potential mechanism for acquired Erbitux (cetuximab) resistance in a colorectal cancer patient, which is consistent with cell culture studies demonstrating moderate resistance to Erbitux (cetuximab) and Fluorouracil combination treatment in colorectal cancer cells over expressing PIK3CA V952A (PMID: 28424201). 28424201
PIK3CA K966E colorectal cancer resistant Cetuximab + Fluorouracil Clinical Study - Cohort Actionable In a clinical study, PIK3CA K966E was identified as a potential mechanism for acquired Erbitux (cetuximab) resistance in a colorectal cancer patient, which is supported by cell culture studies demonstrating resistance to Erbitux (cetuximab) and Fluorouracil combination treatment in colorectal cancer cells overexpressing PIK3CA K966E (PMID: 28424201). 28424201
PIK3CA H450_P458del breast cancer sensitive Alpelisib Preclinical - Cell culture Actionable In a preclinical study, transformed breast epithelial cells expressing PIK3CA H450_P458del were sensitive to treatment with Alpelisib (BYL719) in culture, demonstrating growth inhibition and decreased invasiveness of acini (PMID: 29284706). 29284706
ERBB2 A775_G776insYVMA PIK3CA R425L lung non-small cell carcinoma predicted - resistant Trastuzumab Case Reports/Case Series Actionable In a clinical study, the PIK3CA R425L mutation was identified as a potential resistance mechanism in a non-small cell lung carcinoma patient harboring ERBB2 (HER2) A775_G776insYVMA, that progressed during Herceptin (trastuzumab) treatment (PMID: 28167203). 28167203
PIK3CA E545K Advanced Solid Tumor sensitive Alpelisib Preclinical - Pdx Actionable In a preclinical study, Alpelisib (BYL719) inhibited PIK3CA E545K and showed anti-tumor activity in patient-derived xenograft models harboring a PIK3CA E545K mutation (PMID: 24608574). 24608574
PIK3CA E545K lung squamous cell carcinoma no benefit Taselisib Case Reports/Case Series Actionable In a Phase I (SWOG S1400B) trial, Taselisib (GDC-0032) treatment did not meet primary endpoint in patients with lung squamous cell carcinoma harboring PIK3CA mutations, only 1 of the 11 patients harboring PIK3CA E545K demonstrated response (PMID: 31158500; NCT02785913). 31158500
PIK3CA E545K breast cancer sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA E545K in culture (PMID: 26627007). 26627007
PIK3CA E545K Advanced Solid Tumor resistant A66 Preclinical Actionable In a preclinical study, cancer cell lines harboring PIK3CA E545K did not demonstrate sensitivity to A66 in culture, in contrast with cells harboring PIK3CA H1047R (PMID: 21668414). 21668414
PIK3CA E545K urinary bladder cancer sensitive Gemcitabine + Pictilisib Preclinical - Cell culture Actionable In a preclinical study, Pictilisib (GDC-0941) and Gemzar (gemcitabine) synergistically inhibited Akt phosphorylation and growth of bladder cancer cells harboring PIK3CA E545K in culture (PMID: 28808038). 28808038
PIK3CA E545K urinary bladder cancer sensitive Pictilisib + Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Pictilisib (GDC-0941) and Nexavar (sorafenib) synergistically decreased Erk and Akt phosphorylation, inhibited survival of bladder cancer cells harboring PIK3CA E545K in culture (PMID: 28808038). 28808038
PIK3CA E545K colon cancer sensitive LY2780301 Phase I Actionable In a Phase I trial, a colon cancer patient harboring PIK3CA E545K was sensitive to LY2780301, demonstrating stable disease for approximately 125 days (PMID: 25902900). 25902900
PIK3CA E545K breast cancer sensitive Neratinib Preclinical Actionable In a preclinical study, Nerlynx (neratinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA E545K in culture (PMID: 26627007). 26627007
PIK3CA E545K lung squamous cell carcinoma sensitive Alpelisib Preclinical - Cell culture Actionable In a preclinical study, Alpelisib (BYL719) induced apoptosis, inhibited cell proliferation, migration, and invasion of lung squamous cell carcinoma cells over expressing PIK3CA E545K in culture (PMID: 26013318). 26013318
PIK3CA E545K breast cancer predicted - sensitive Dactolisib + WEHI-539 Preclinical - Cell culture Actionable In a preclinical study, inhibition of Pi3k signaling by BEZ235 sensitized breast cancer cell lines harboring PIK3CA E545K to WEHI-539 in culture (PMID: 27974663). 27974663
PIK3CA E545K breast cancer sensitive Borussertib Preclinical - Cell culture Actionable In a preclinical study, borussertib inhibited AKT signaling and proliferation of a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 30858154). 30858154
PIK3CA E545K Her2-receptor negative breast cancer no benefit Everolimus Phase III Actionable In a retrospective analysis of a Phase III trial (BOLERO-2), Afinitor (everolimus) demonstrated comparable progression-free survival benefit in patients with hormone receptor-positive, Erbb2 (Her2)-negative breast cancer harboring wild-type (HR=0.43) or mutant (HR=0.37) PIK3CA, similar benefit was observed in subgroups harboring PIK3CA H1047R (HR=0.37) and PIK3CA E545K/E542K (HR=0.30) (PMID: 28183140; NCT00863655). 28183140
PIK3CA E545K breast cancer predicted - sensitive CYH33 Preclinical - Cell culture Actionable In a preclinical study, CYH33 inhibited proliferation of a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 30003928). 30003928
PIK3CA E545K breast cancer sensitive DHM25 Preclinical - Cell culture Actionable In a preclinical study, DHM25 increased cell death in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 26237138). 26237138
PIK3CA E545K Advanced Solid Tumor sensitive Rigosertib Sodium Preclinical - Cell culture Actionable In a preclinical study, Rigosertib (ON 01910.Na) inhibited oncogenic transformation in fibroblast cells over-expressing PIK3CA E545K in culture (PMID: 27104980). 27104980
PIK3CA E545K colorectal cancer sensitive Dactolisib Preclinical Actionable In a preclinical study, BEZ235 decreased cell proliferation in colorectal cancer cells harboring a PIK3CA E545K mutation in cell culture (PMID: 21966435). 21966435
PIK3CA E545K ovarian cancer sensitive CH5132799 Preclinical Actionable In a preclinical study, CH5132799 inhibited proliferation of ovarian cancer cells harboring PIK3CA E545K in culture (PMID: 21558396). 21558396
PIK3CA E545K head and neck squamous cell carcinoma predicted - sensitive Carboplatin + Paclitaxel + Temsirolimus Case Reports/Case Series Actionable In a Phase II trial, a patient with head and neck squamous cell carcinoma harboring PIK3CA E545K demonstrated a partial response when treated with the combination of Torisel (temsirolimus), Paraplatin (carboplatin), and Taxol (paclitaxel) (PMID: 28961834). 28961834
PIK3CA E545K Advanced Solid Tumor sensitive GDC-0980 Phase I Actionable In a Phase I trial, Apitolisib (GDC-0980) resulted in a partial response in two patients, one with head and neck squamous cell carcinoma and another with ovarian cancer, both harboring PIK3CA E545K (PMID: 26787751). 26787751
PIK3CA E545K lung squamous cell carcinoma sensitive Dactolisib Preclinical - Cell culture Actionable In a preclinical study, BEZ235 induced apoptosis, inhibited cell proliferation, migration, and invasion of lung squamous cell carcinoma cells over expressing PIK3CA E545K in culture (PMID: 26013318). 26013318
PIK3CA E545K breast cancer sensitive CH5132799 Preclinical Actionable In a preclinical study, CH5132799 inhibited proliferation of breast cancer cells expressing PIK3CA E545K (PMID: 21558396). 21558396
PIK3CA E545K breast cancer sensitive MK2206 Preclinical Actionable In a preclinical study, MK2206 inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA E545K in culture (PMID: 26627007). 26627007
PIK3CA E545K Advanced Solid Tumor sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited survival of transformed cell lines overexpressing PIK3CA E545K in culture (PMID: 26627007). 26627007
PIK3CA E545K breast cancer sensitive Dactolisib Preclinical Actionable In a preclinical study, BEZ235 inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA E545K in culture (PMID: 26627007). 26627007
PIK3CA E545K breast carcinoma sensitive XL147 Preclinical - Cell line xenograft Actionable In a preclinical study, XL147 inhibited PI3K signaling and proliferation of a human breast carcinoma cell line harboring PIK3CA E545K in culture and inhibited tumor growth in xenograft models (PMID: 25637314). 25637314
PIK3CA E545K breast cancer sensitive Ipatasertib Preclinical - Cell line xenograft Actionable In a preclinical study, Ipatasertib (GDC-0068) demonstrated activity against tumor growth in cell line xenograft models of breast cancer cells harboring PIK3CA E545K (PMID: 32205017). 32205017
PIK3CA E545K colorectal cancer sensitive Cetuximab + Irinotecan Case Reports/Case Series Actionable In a retrospective analysis, treatment with the combination of Erbitux (cetuximab) and Camptosar (irinotecan) resulted in stable disease in 50% (1/2) and 14 months without evidence of disease in 50% (1/2) of colorectal carcinoma patients harboring a PIK3CA E545K mutation (PMID: 25714871). 25714871
PIK3CA E545K breast cancer sensitive Ipatasertib + Paclitaxel Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Ipatasertib (GDC-0068) and Taxol (paclitaxel) synergistically inhibited tumor growth in cell line xenograft models of breast cancer cells harboring PIK3CA E545K (PMID: 32205017). 32205017
PIK3CA E545K head and neck squamous cell carcinoma sensitive Rigosertib Sodium Preclinical - Pdx Actionable In a preclinical study, head and neck squamous cell carcinoma patient-derived xenograft models harboring a PIK3CA E545K mutation demonstrated increased sensitivity to Rigosertib (ON 01910.Na) (PMID: 23873848). 23873848
PIK3CA E545K breast cancer resistant Buparlisib Preclinical - Cell culture Actionable In a preclinical study, breast cancer cells expressing PIK3CA E545K demonstrated resistance to treatment with Buparlisib (BKM120) in culture (PMID: 29636477). 29636477
PIK3CA E545K thyroid gland cancer sensitive MK2206 Preclinical - Cell culture Actionable In a preclinical study, expression of PIK3CA E545K in a thyroid cancer cell line resulted in increased sensitivity to MK2206 in culture (PMID: 21289267). 21289267
PIK3CA E545K breast cancer sensitive Gedatolisib Preclinical Actionable In a preclinical study, Gedatolisib (PKI-587) inhibited growth of human breast cancer cells harboring PIK3CA E545K in culture (PMID: 21325073, PMID: 17314276). 17314276 21325073
PIK3CA E545K colorectal cancer resistant Cetuximab + Fluorouracil Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells over expressing PIK3CA E545K were resistant to Erbitux (cetuximab) and Fluorouracil combination treatment in culture (PMID: 28424201). 28424201
PIK3CA E545K esophagus squamous cell carcinoma sensitive LY294002 Preclinical Actionable In a preclinical study, LY294002 inhibited cell proliferation of esophagus squamous cell carcinoma cells expressing PIK3CA E545K (PMID: 18262558). 18262558
PIK3CA E545K leukemia sensitive LY3023414 Preclinical Actionable In a preclinical study, LY3023414 inhibited tumor growth in a transgenic animal model of leukemia driven by PIK3CA E545K (PMID: 27439478). 27439478
PIK3CA E545K lung non-small cell carcinoma sensitive Copanlisib + Paclitaxel Preclinical - Pdx Actionable In a preclinical study, Aliqopa (copanlisib), in combination with Taxol (paclitaxel), induced tumor regression in PIK3CA E545K-mutant patient-derived non-small cell lung cancer xenografts (PMID: 24170767). 24170767
PIK3CA E545K breast cancer sensitive Voxtalisib Preclinical - Cell line xenograft Actionable In a preclinical study, a breast cancer cell line harboring PIK3CA E545K was sensitive to XL765 (SAR245409), demonstrating inhibition of cell proliferation and colony formation in culture, and inhibition of tumor growth in cell line xenograft models (PMID: 24634413). 24634413
PIK3CA E545K urinary bladder cancer sensitive Cisplatin + Pictilisib Preclinical - Cell culture Actionable In a preclinical study, Pictilisib (GDC-0941) and Platinol (cisplatin) synergistically inhibited Akt phosphorylation and growth of bladder cancer cells harboring PIK3CA E545K in culture (PMID: 28808038). 28808038
PIK3CA E545K Advanced Solid Tumor sensitive Sirolimus Preclinical Actionable In a preclinical study, Rapamune (sirolimus) demonstrated efficacy in inhibiting transformation of cultured cells containing PIK3CA E545K mutations (PMID: 15647370). 15647370
PIK3CA E545K breast cancer sensitive PKI-402 Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with PKI-402 resulted in decreased Akt phosphorylation and tumor regression in ERBB2 (HER2)-positive breast cancer cell line xenograft models harboring PIK3CA E545K (PMID: 20371716). 20371716
PIK3CA E545K cervical cancer sensitive PW12 Preclinical Actionable In a preclinical study, PW12 inhibited proliferation of cervical cancer cells with a PIK3CA E545K mutation (PMID: 22391131). 22391131
PIK3CA E545K gastrointestinal system cancer sensitive Capivasertib Preclinical Actionable In a preclinical study, gastric cancer cells harboring PI3KCA E545K mutations were sensitive to the AKT inhibitor AZD5363 (PMID: 24088382). 24088382
PIK3CA E545K urinary bladder cancer sensitive Pictilisib Preclinical - Cell culture Actionable In a preclinical study, Pictilisib (GDC-0941) inhibited Akt phosphorylation, resulted in growth inhibition in bladder cancer cells harboring PIK3CA E545K in culture (PMID: 28808038). 28808038
PIK3CA E545K breast cancer sensitive WYE-125132 Preclinical Actionable In a preclinical study, WYE-125132 inhibited proliferation of breast cancer cells with a PIK3CA E545K mutation (PMID: 20068177). 20068177
PIK3CA E545K lung squamous cell carcinoma sensitive Buparlisib Preclinical - Cell culture Actionable In a preclinical study, Buparlisib (BKM120) induced apoptosis, inhibited cell proliferation, migration, and invasion of lung squamous cell carcinoma cells over expressing PIK3CA E545K in culture (PMID: 26013318). 26013318
PIK3CA E545K breast cancer sensitive Lapatinib Preclinical Actionable In a preclinical study, Tykerb (lapatinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA E545K in culture (PMID: 26627007). 26627007
PIK3CA E545K breast cancer sensitive Miransertib Preclinical - Cell culture Actionable In a preclinical study, treatment with Miransertib (ARQ092) resulted in growth inhibition in hormone receptor positive breast cancer cells harboring PIK3CA E545K in culture (PMID: 26469692). 26469692
PIK3CA E545K stomach cancer sensitive Capivasertib Preclinical - Cell culture Actionable In a preclinical study, a gastric cancer cell line harboring PIK3CA E545K was sensitive to treatment with Capivasertib (AZD5363), demonstrating decreased cell proliferation in culture (PMID: 32070411). 32070411
PIK3CA E545K breast cancer sensitive Alpelisib Preclinical - Cell culture Actionable In a preclinical study, Alpelisib (BYL719) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA E545K in culture (PMID: 26627007). 26627007
PIK3CA E545K Klatskin's tumor unknown Sirolimus Phase 0 Actionable In a pilot clinical trial, Rapamune (sirolimus) demonstrated modest clinical activity in patients with PIK3CA-mutant gastric cancer (n=3) or hilar cholangiocarcinoma (n=1; harboring PIK3CA E545K), with a 0% response rate, median progression-free survival of 1.9 months, and median overall survival of 3.6 months (PMID: 28685070). 28685070
PIK3CA E545K breast cancer no benefit Dactolisib + Venetoclax Preclinical - Cell culture Actionable In a preclinical study, inhibition of Pi3k signaling by BEZ235 did not sensitize breast cancer cell lines harboring PIK3CA E545K to Venclexta (venetoclax) in culture (PMID: 27974663). 27974663
PIK3CA E545K breast cancer sensitive BAY1125976 Preclinical - Cell line xenograft Actionable In a preclinical study, BAY1125976 inhibited proliferation of a breast cancer cell line harboring PIK3CA E545K in culture, and inhibited AKT signaling and tumor growth in xenograft models (PMID: 27699769). 27699769
PIK3CA E545K estrogen-receptor positive breast cancer sensitive AZD8835 Preclinical Actionable In a preclinical study, AZD8835 inhibited proliferation of estrogen receptor (ER)-positive breast cancer cells harboring PIK3CA E545K in culture and suppressed tumor growth in xenograft models (PMID: 26839307). 26839307
PIK3CA E545K breast cancer sensitive ARQ 751 Preclinical - Cell culture Actionable In a preclinical study, a breast cancer cell line harboring PIK3CA E545K was sensitive to ARQ 751 in culture, demonstrating inhibition of cell growth (PMID: 26469692). 26469692
PIK3CA E545K breast cancer sensitive Everolimus Preclinical Actionable In a preclinical study, breast cancer cell lines harboring a PIK3CA E545K mutation had increased sensitivity to Afinitor (everolimus) in culture (PMID: 20664172). 20664172
PIK3CA E545K lung non-small cell carcinoma sensitive T-2143 Preclinical - Cell line xenograft Actionable In a preclinical study, T-2143 treatment reduced proliferation of non-small cell lung cancer cells harboring PIK3CA E545K in culture, and inhibited tumor growth in a cell line xenograft model (PMID: 32499300). 32499300
ERBB2 amp PIK3CA E545K breast cancer sensitive Buparlisib Preclinical - Cell line xenograft Actionable In a preclinical study, a breast cancer cell line xenograft model co-harboring ERBB2 (HER2) amplification and PIK3CA E545K demonstrated tumor regression within the mammary fat pad when treated with Buparlisib (BKM120) (PMID: 28539475). 28539475
ERBB2 amp PIK3CA E545K breast cancer predicted - sensitive CYH33 Preclinical - Cell culture Actionable In a preclinical study, CYH33 inhibited proliferation of a breast cancer cell line harboring PIK3CA E545K and ERBB2 (HER2) amplification in culture (PMID: 30003928). 30003928
ERBB2 amp PIK3CA E545K breast cancer sensitive CH5132799 Preclinical Actionable In a preclinical study, CH5132799 inhibited proliferation of a breast cancer cell line harboring PIK3CA E545K and ERBB2 (HER2) amplification in culture (PMID: 21558396). 21558396
ERBB2 pos PIK3CA E545K Her2-receptor positive breast cancer predicted - sensitive Neratinib Phase III Actionable In a Phase III trial (ExteNET), Nerlynx (neratinib) treatment resulted in improved 5-year invasive disease-free survival (92.4% vs 84.5%, HR=0.41, p=0.028) and clinical benefit (HR=0.40, p=0.041) compared to placebo in patients with ERBB2 (HER2)-positive early breast cancer who completed trastuzumab-based adjuvant therapy, and harbored PIK3CA amplification (n=61) or mutations (n=210), including H1047R (n=110), E542K (n=18), and E545K/D (n=82) (PMID: 30867034; NCT00878709). 30867034
ERBB2 pos PIK3CA E545K Her2-receptor positive breast cancer sensitive Ado-trastuzumab emtansine Preclinical - Cell line xenograft Actionable In a preclinical study, Kadcyla (trastuzumab emtansine) inhibited survival of Herceptin (trastuzumab)-resistant ERBB2 (HER2) positive breast cancer cells harboring PIK3CA E545K in culture, and induced tumor regression in cell line xenograft models (PMID: 26920887). 26920887
BRAF G596R PIK3CA E545K colorectal cancer sensitive Neratinib Preclinical Actionable In a preclinical study, Nerlynx (neratinib) inhibited growth of colorectal cancer cells harboring both BRAF G596R and PIK3CA E545K in culture (PMID: 26243863). 26243863
BRAF G596R PIK3CA E545K colorectal cancer resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF G596R and PIK3CA E545K did not demonstrate sensitivity to Zelboraf (vemurafenib) treatment in culture (PMID: 22180495). 22180495
AKT1 over exp PIK3CA E545K breast cancer resistant Pictilisib Preclinical - Cell culture Actionable In a preclinical study, Akt1 over expression in breast cancer cells harboring PIK3CA E545K resulted in resistance to Pictilisib (GDC-0941) in culture (PMID: 27604488). 27604488
NRAS mut PIK3CA E545K melanoma predicted - resistant Palbociclib Preclinical - Cell culture Actionable In a preclinical study, two of two NRAS-mutant melanoma cell lines expressing PIK3CA E545K demonstrated resistance to treatment with Ibrance (palbociclib) in culture (PMID: 30819666). 30819666
NRAS mut PIK3CA E545K melanoma predicted - resistant Palbociclib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, four of four NRAS-mutant melanoma cell lines expressing PIK3CA E545K were resistant to the combination treatment of Ibrance (palbociclib) and Mekinist (trametinib) in culture (PMID: 30819666). 30819666
NRAS mut PIK3CA E545K melanoma predicted - resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, NRAS-mutant melanoma cell lines expressing PIK3CA E545K demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 30819666). 30819666
PIK3CA E545K ROS1 rearrange lung non-small cell carcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a Phase II clinical trial, a patient with non-small cell lung cancer harboring a ROS1 rearrangement demonstrated progression while being treated with Xalkori (crizotinib), and was found to have acquired a PIK3CA E545K mutation (PMID: 30978502; NCT02183870). 30978502
PIK3CA E545K PIK3CA E726K breast cancer sensitive GDC-0077 Preclinical - Cell culture Actionable In a preclinical study, breast epithelial cells expressing PIK3CA E545K and PIK3CA E726K in cis demonstrated increased sensitivity to growth inhibition by GDC-0077 treatment compared to cells expressing individual PIK3CA mutations in culture (PMID: 31699932). 31699932
PIK3CA E545K PIK3CA E726K breast cancer sensitive Everolimus Preclinical - Cell culture Actionable In a preclinical study, breast epithelial cells expressing PIK3CA E545K and PIK3CA E726K in cis demonstrated increased sensitivity to growth inhibition by Afinitor (everolimus) treatment compared to cells expressing individual PIK3CA mutations in culture (PMID: 31699932). 31699932
PIK3CA E545K PIK3CA E726K breast cancer sensitive Alpelisib Preclinical - Cell culture Actionable In a preclinical study, breast epithelial cells expressing PIK3CA E545K and PIK3CA E726K in cis demonstrated increased sensitivity to growth inhibition by Piqray (Alpelisib) treatment compared to cells expressing individual PIK3CA mutations in culture (PMID: 31699932). 31699932
PIK3CA E545K PIK3CA M1043L breast cancer sensitive Alpelisib Preclinical - Cell culture Actionable ??In a preclinical study, breast epithelial cells expressing PIK3CA E545K and PIK3CA M1043L in cis demonstrated increased sensitivity to growth inhibition by Piqray (Alpelisib) treatment compared to cells expressing individual PIK3CA mutations in culture (PMID: 31699932). 31699932
PIK3CA E545K PIK3CA M1043L breast cancer sensitive GDC-0077 Preclinical - Cell culture Actionable In a preclinical study, breast epithelial cells expressing PIK3CA E545K and PIK3CA M1043L in cis demonstrated increased sensitivity to growth inhibition by GDC-0077 treatment compared to cells expressing individual PIK3CA mutations in culture (PMID: 31699932). 31699932
PIK3CA E545K PIK3CA M1043L breast cancer sensitive Everolimus Preclinical - Cell culture Actionable In a preclinical study, breast epithelial cells expressing PIK3CA E545K and PIK3CA M1043L in cis demonstrated increased sensitivity to growth inhibition by Afinitor (everolimus) treatment compared to cells expressing individual PIK3CA mutations in culture (PMID: 31699932). 31699932
PIK3CA R88Q colorectal cancer predicted - sensitive Cetuximab + Floxuridine + Fluorouracil + Irinotecan Case Reports/Case Series Actionable In a retrospective analysis, treatment with the combination of Erbitux (cetuximab), Adrucil (fluorouracil), Camptosar (irinotecan), and Floxuridine resulted in at least 24 months without evidence of disease in a colorectal carcinoma patient harboring a PIK3CA R88Q mutation (PMID: 25714871). 25714871
PIK3CA R88Q malignant pleural mesothelioma sensitive GDC-0980 Phase I Actionable In a Phase I trial, treatment with Apitolisib (GDC-0980) resulted in a partial response in a patient with malignant pleural mesothelioma harboring PIK3CA R88Q (PMID: 26787751). 26787751
PIK3CA R88Q malignant glioma sensitive Buparlisib + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Buparlisib (BKM120) and Koselugo (selumetinib) led to a synergistic effect, resulting in greater growth inhibition of astrocytoma cells expressing PIK3CA R88Q than cells with wild-type PIK3CA in culture (PMID: 29975751). 29975751
HRAS mut PIK3CA R88Q malignant glioma sensitive Buparlisib + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Buparlisib (BKM120) and Koselugo (selumetinib) led to a synergistic effect, resulting in growth inhibition of astrocytoma cells with an HRAS mutation and expressing PIK3CA R88Q in culture, but at a higher drug concentration compared to cells without mutant HRAS (PMID: 29975751). 29975751
PIK3CA E39K breast cancer resistant Buparlisib Preclinical - Cell culture Actionable In a preclinical study, breast cancer cells expressing PIK3CA E39K demonstrated resistance to treatment with Buparlisib (BKM120) in culture (PMID: 29636477). 29636477
PIK3CA exon21 Her2-receptor negative breast cancer no benefit Everolimus Phase III Actionable In a retrospective analysis of a Phase III trial (BOLERO-2), Afinitor (everolimus) demonstrated greater benefit on progression-free survival in patients with hormone receptor-positive, Erbb2 (Her2)-negative breast cancer harboring PIK3CA exon 10 (reported as exon 9) mutations (HR=0.26) compared to patients harboring PIK3CA exon 21 (reported as exon 20) mutations (HR=0.56) (PMID: 26503204; NCT00863655). 26503204
PIK3CA R38C head and neck squamous cell carcinoma sensitive Sulindac Preclinical - Pdx Actionable In a preclinical study, Clinoril (sulindac) treatment reduced tumor growth rate in patient-derived xenograft (PDX) models of head and neck squamous cell carcinoma harboring PIK3CA mutations, including PIK3CA R38C (PMID: 30683736). 30683736
PIK3CA Q546K breast cancer sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA Q546K in culture (PMID: 26627007). 26627007
PIK3CA Q546K breast cancer sensitive Neratinib Preclinical Actionable In a preclinical study, Nerlynx (neratinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA Q546K in culture (PMID: 26627007). 26627007
PIK3CA Q546K breast cancer sensitive MK2206 Preclinical Actionable In a preclinical study, MK2206 inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA Q546K in culture (PMID: 26627007). 26627007
PIK3CA Q546K breast cancer sensitive Alpelisib Preclinical - Cell culture Actionable In a preclinical study, Alpelisib (BYL719) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA Q546K in culture (PMID: 26627007). 26627007
PIK3CA Q546K breast cancer sensitive Lapatinib Preclinical Actionable In a preclinical study, Tykerb (lapatinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA Q546K in culture (PMID: 26627007). 26627007
PIK3CA Q546K Advanced Solid Tumor sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited survival of transformed cell lines overexpressing PIK3CA Q546K in culture (PMID: 26627007). 26627007
PIK3CA Q546K breast cancer sensitive Dactolisib Preclinical Actionable In a preclinical study, BEZ235 inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA Q546K in culture (PMID: 26627007). 26627007
PIK3CA I391M uterine cancer predicted - sensitive Sirolimus Case Reports/Case Series Actionable In a clinical case study, a uterine cancer patient harboring PIK3CA I391M demonstrated stable disease when treated with Rapamune (sirolimus) (PMID: 28514312). 28514312
ERBB2 pos PIK3CA I391M Her2-receptor positive breast cancer sensitive Ado-trastuzumab emtansine Preclinical - Cell culture Actionable In a preclinical study, Kadcyla (trastuzumab emtansine) inhibited survival of ERBB2 (HER2) positive breast cancer cells harboring PIK3CA K111N in culture (PMID: 26920887). 26920887
PIK3CA H1047L breast cancer sensitive Lapatinib Preclinical Actionable In a preclinical study, Tykerb (lapatinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA H1047L in culture (PMID: 26627007). 26627007
PIK3CA H1047L breast cancer sensitive Neratinib Preclinical Actionable In a preclinical study, Nerlynx (neratinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA H1047L in culture (PMID: 26627007). 26627007
PIK3CA H1047L breast cancer sensitive Dactolisib Preclinical Actionable In a preclinical study, BEZ235 inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA H1047L in culture (PMID: 26627007). 26627007
PIK3CA H1047L oral squamous cell carcinoma decreased response Palbociclib Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with Ibrance (palbociclib) resulted in sustained tumor growth, but increasing tumor volume over time with treatment in oral squamous cell carcinoma cell line xenograft models harboring PIK3CA H1047L (PMID: 31516747). 31516747
PIK3CA H1047L breast cancer sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA H1047L in culture (PMID: 26627007). 26627007
PIK3CA H1047L oral squamous cell carcinoma predicted - sensitive PF-04691502 Preclinical - Cell line xenograft Actionable In a preclinical study, PF-04691502 treatment inhibited tumor growth in a cell line xenograft model of oral squamous cell carcinoma harboring PIK3CA H1047L (PMID: 31516747). 31516747
PIK3CA H1047L oral squamous cell carcinoma sensitive Palbociclib + PF-04691502 Preclinical - Cell line xenograft Actionable In a preclinical study, oral squamous cell carcinoma cells harboring PIK3CA H1047L demonstrated increased sensitivity to Ibrance (palbociclib) when combined with PF-04691502, and the combination treatment inhibited proliferation in cell culture, and reduced tumor growth in a cell line xenograft model (PMID: 31516747). 31516747
PIK3CA H1047L breast cancer sensitive Alpelisib Preclinical - Cell culture Actionable In a preclinical study, Alpelisib (BYL719) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA H1047L in culture (PMID: 26627007). 26627007
PIK3CA H1047L breast cancer sensitive MK2206 Preclinical Actionable In a preclinical study, MK2206 inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA H1047L in culture (PMID: 26627007). 26627007
ERBB2 over exp PIK3CA H1047L stomach cancer predicted - resistant Trastuzumab Clinical Study - Cohort Actionable In a clinical study (AMNESIA-1), assessment of pre-treatment tumor samples from ERBB2 (HER2)-positive gastric or gastroesophageal cancer patients (defined as HER2 IHC 3+ or HER2 IHC 2+/ISH+) identified PIK3CA mutations in 15% (3/20) of patients demonstrating primary resistance to Herceptin (trastuzumab), including 1 patient harboring PIK3CA H1047L (PMID: 29208673). 29208673
PIK3CA E453K breast cancer resistant Buparlisib Preclinical - Cell culture Actionable In a preclinical study, breast cancer cells expressing PIK3CA E453K demonstrated resistance to treatment with Buparlisib (BKM120) in culture (PMID: 29636477). 29636477
PIK3CA E453K lung squamous cell carcinoma no benefit Taselisib Case Reports/Case Series Actionable In a Phase I (SWOG S1400B) trial, Taselisib (GDC-0032) treatment did not meet primary endpoint in patients with lung squamous cell carcinoma harboring PIK3CA mutations, a patients harboring PIK3CA E453K did not demonstrated response (PMID: 31158500; NCT02785913). 31158500
PIK3CA V955G colorectal cancer resistant Cetuximab + Fluorouracil Case Reports/Case Series Actionable In a clinical study, PIK3CA V955G was identified as a potential mechanism for acquired Erbitux (cetuximab) resistance in a colorectal cancer patient, which is supported by cell culture studies demonstrating resistance to Erbitux (cetuximab) and Fluorouracil combination treatment in colorectal cancer cells over expressing PIK3CA V955G (PMID: 28424201). 28424201
PIK3CA N345K Advanced Solid Tumor sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited survival of transformed cell lines overexpressing PIK3CA N345K in culture (PMID: 26627007). 26627007
PIK3CA N345K breast cancer sensitive Alpelisib Preclinical - Cell culture Actionable In a preclinical study, Alpelisib (BYL719) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA N345K in culture (PMID: 26627007). 26627007
PIK3CA N345K breast cancer sensitive Dactolisib Preclinical Actionable In a preclinical study, BEZ235 inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA N345K in culture (PMID: 26627007). 26627007
PIK3CA N345K breast cancer sensitive Neratinib Preclinical Actionable In a preclinical study, Nerlynx (neratinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA N345K in culture (PMID: 26627007). 26627007
PIK3CA N345K breast cancer sensitive MK2206 Preclinical Actionable In a preclinical study, MK2206 inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA N345K in culture (PMID: 26627007). 26627007
PIK3CA N345K lung squamous cell carcinoma no benefit Taselisib Case Reports/Case Series Actionable In a Phase I (SWOG S1400B) trial, Taselisib (GDC-0032) treatment did not meet primary endpoint in patients with lung squamous cell carcinoma harboring PIK3CA mutations, none of the 2 patients harboring PIK3CA N345K demonstrated response (PMID: 31158500; NCT02785913). 31158500
PIK3CA N345K breast cancer sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA N345K in culture (PMID: 26627007). 26627007
PIK3CA N345K breast cancer sensitive Lapatinib Preclinical Actionable In a preclinical study, Tykerb (lapatinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA N345K in culture (PMID: 26627007). 26627007
PIK3CA N345K endometrial mixed adenocarcinoma no benefit Copanlisib Case Reports/Case Series Actionable In a Phase II (NRG-GY008) trial, Aliqopa (copanlisib) was well tolerated but demonstrated limited efficacy, resulted in stable disease in a patient with endometrial mixed adenocarcinoma harboring PIK3CA N345K (PMID: 31934607). 31934607
ERBB2 amp PIK3CA N345K breast cancer sensitive CH5132799 Preclinical Actionable In a preclinical study, CH5132799 inhibited proliferation of a breast cancer cell line harboring PIK3CA N345K and ERBB2 (HER2) amplification in culture (PMID: 21558396). 21558396
PIK3CA E545V ovarian clear cell adenocarcinoma sensitive DS-7423 Preclinical - Cell culture Actionable In a preclinical study, an ovarian clear cell adenocarcinoma cell line harboring PIK3CA E545V was sensitive to DS-7423 in culture, demonstrating inhibition of cell proliferation (PMID: 24504419). 24504419
PIK3CA C420R ovarian clear cell adenocarcinoma sensitive DS-7423 Preclinical - Cell culture Actionable In a preclinical study, an ovarian clear cell adenocarcinoma cell line harboring PIK3CA C420R was sensitive to DS-7423 in culture, demonstrating inhibition of cell proliferation (PMID: 24504419). 24504419
PIK3CA C420R Advanced Solid Tumor sensitive Sirolimus Preclinical Actionable In a preclinical study, cells expressing PIK3CA C420R were sensitive to Rapamune (sirolimus) in culture (PMID: 17376864). 17376864
ERBB2 amp PIK3CA C420R breast cancer sensitive CYH33 Preclinical - Cell culture Actionable In a preclinical study, CYH33 inhibited proliferation of breast cancer cell lines harboring PIK3CA C420R and ERBB2 (HER2) amplification in culture (PMID: 30003928). 30003928
ERBB2 amp PIK3CA C420R breast cancer sensitive CH5132799 Preclinical Actionable In a preclinical study, CH5132799 inhibited proliferation of a breast cancer cell line harboring PIK3CA C420R and ERBB2 (HER2) amplification (PMID: 21558396). 21558396
ERBB2 pos PIK3CA C420R Her2-receptor positive breast cancer sensitive Ado-trastuzumab emtansine Preclinical - Cell culture Actionable In a preclinical study, Kadcyla (trastuzumab emtansine) inhibited survival of ERBB2 (HER2) positive breast cancer cells harboring PIK3CA C420R in culture (PMID: 26920887). 26920887
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