Gene Variant Detail

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Gene PIK3CA
Variant act mut
Impact List unknown
Protein Effect gain of function
Gene Variant Descriptions PIK3CA act mut indicates that this variant results in a gain of function in the Pik3ca protein. However, the specific amino acid change has not been identified.
Associated Drug Resistance

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No Variant Reference Transcript is Available.
No transcript is Available.

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
PIK3CA act mut ovarian clear cell adenocarcinoma sensitive BEZ235 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 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 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 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
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 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 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 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 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 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 breast cancer no benefit BEZ235 + 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 breast cancer predicted - sensitive BEZ235 + 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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
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 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 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 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 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