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| Profile Name | PIK3CA E545K |
| Gene Variant Detail | |
| Relevant Treatment Approaches | Akt Inhibitor (Pan) Akt1 Inhibitor Akt2 Inhibitor mTOR Inhibitor mTORC1 Inhibitor mTORC2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor |
| Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|---|
| PIK3CA E545K | lung non-small cell carcinoma | sensitive | PIK3CA inhibitor | 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 | Advanced Solid Tumor | sensitive | mTORC1 Inhibitor | 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 | gastrointestinal system cancer | sensitive | Akt Inhibitor (Pan) | Capivasertib | Preclinical - Cell culture | Actionable | In a preclinical study, gastric cancer cells harboring PIK3CA E545K demonstrated sensitivity to the AKT inhibitor Truqap (capivasertib), resulting in decreased proliferation in culture (PMID: 24088382). | 24088382 |
| PIK3CA E545K | breast cancer | sensitive | mTORC1 Inhibitor | 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 | colorectal cancer | sensitive | mTOR Inhibitor PI3K Inhibitor (Pan) | 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 | Advanced Solid Tumor | sensitive | PIK3CA inhibitor | 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 | head and neck squamous cell carcinoma | sensitive | PI3K Inhibitor (Pan) | 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 | Advanced Solid Tumor | resistant | PIK3CA inhibitor | 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 | esophagus squamous cell carcinoma | sensitive | PI3K Inhibitor (Pan) | 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 | cervical cancer | sensitive | PIK3CA inhibitor | PW12 | Preclinical | Actionable | In a preclinical study, PW12 inhibited proliferation of cervical cancer cells with a PIK3CA E545K mutation (PMID: 22391131). | 22391131 |
| PIK3CA E545K | breast cancer | sensitive | mTOR Inhibitor | 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 | breast cancer | sensitive | PI3K Inhibitor (Pan) | MEN1611 | Preclinical | Actionable | In a preclinical study, MEN1611 (CH5132799) inhibited proliferation of breast cancer cells expressing PIK3CA E545K (PMID: 21558396). | 21558396 |
| PIK3CA E545K | ovarian cancer | sensitive | PI3K Inhibitor (Pan) | MEN1611 | Preclinical | Actionable | In a preclinical study, MEN1611 (CH5132799) inhibited proliferation of ovarian cancer cells harboring PIK3CA E545K in culture (PMID: 21558396). | 21558396 |
| PIK3CA E545K | breast cancer | sensitive | mTOR Inhibitor PI3K Inhibitor (Pan) | 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 | 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 | mTOR Inhibitor PI3K Inhibitor (Pan) | 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 cancer | sensitive | PIK3CA inhibitor | 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 | breast cancer | sensitive | Akt Inhibitor (Pan) | 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 | 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 | 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 | 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 | 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 | estrogen-receptor positive breast cancer | sensitive | PIK3CA inhibitor | 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 | mTOR Inhibitor PI3K Inhibitor (Pan) | 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 | head and neck squamous cell carcinoma | predicted - sensitive | mTOR Inhibitor PI3K Inhibitor (Pan) | Apitolisib | Case Reports/Case Series | Actionable | In a Phase I trial, Apitolisib (GDC-0980) treatment resulted in an unconfirmed partial response in a patient with head and neck squamous cell carcinoma harboring PIK3CA E545K (PMID: 26787751; NCT00854152). | 26787751 |
| PIK3CA E545K | ovarian clear cell carcinoma | predicted - sensitive | mTOR Inhibitor PI3K Inhibitor (Pan) | Apitolisib | Case Reports/Case Series | Actionable | In a Phase I trial, Apitolisib (GDC-0980) treatment resulted in tumor regression by 48.3% in a patient with ovarian clear cell carcinoma harboring PIK3CA E545K, who remained on treatment for 282 days (PMID: 26787751; NCT00854152). | 26787751 |
| PIK3CA E545K | breast carcinoma | sensitive | PI3K Inhibitor (Pan) | 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 | lung squamous cell carcinoma | sensitive | PI3K Inhibitor (Pan) | 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 | lung squamous cell carcinoma | sensitive | mTOR Inhibitor PI3K Inhibitor (Pan) | 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 | lung squamous cell carcinoma | sensitive | PIK3CA inhibitor | 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 | thyroid cancer | sensitive | Akt Inhibitor (Pan) | 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 | Advanced Solid Tumor | sensitive | PI3K Inhibitor (Pan) | 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 | breast cancer | sensitive | Akt1 Inhibitor Akt2 Inhibitor | 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 | leukemia | sensitive | mTOR Inhibitor PI3K Inhibitor (Pan) | 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 | breast cancer | no benefit | mTOR Inhibitor PI3K Inhibitor (Pan) | 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 | predicted - sensitive | mTOR Inhibitor PI3K Inhibitor (Pan) | 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 | Akt Inhibitor (Pan) | 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 | breast cancer | sensitive | Akt Inhibitor (Pan) | 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 | colon cancer | predicted - sensitive | Akt Inhibitor (Pan) | LY2780301 | Case Reports/Case Series | 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 | mTOR Inhibitor | 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 | breast cancer | sensitive | mTOR Inhibitor PI3K Inhibitor (Pan) | 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 | 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 | head and neck squamous cell carcinoma | predicted - sensitive | mTORC1 Inhibitor | 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 | Klatskin's tumor | unknown | mTORC1 Inhibitor | 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 | urinary bladder cancer | sensitive | PI3K Inhibitor (Pan) | 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 | urinary bladder cancer | sensitive | PI3K Inhibitor (Pan) | 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 | urinary bladder cancer | sensitive | PI3K Inhibitor (Pan) | 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 | PI3K Inhibitor (Pan) | 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 | breast cancer | resistant | PI3K Inhibitor (Pan) | 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 | lung squamous cell carcinoma | no benefit | PIK3CA inhibitor | Taselisib | Case Reports/Case Series | Actionable | In a Phase I (SWOG S1400B) trial, Taselisib (GDC-0032) treatment did not meet its primary endpoint for response rate in patients with lung squamous cell carcinoma harboring PIK3CA mutations, resulting in only 1 response of 11 patients harboring PIK3CA E545K (PMID: 31158500; NCT02785913). | 31158500 |
| PIK3CA E545K | breast cancer | predicted - sensitive | PIK3CA inhibitor | 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 | Her2-receptor negative breast cancer | no benefit | mTORC1 Inhibitor | 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 | sensitive | Akt1 Inhibitor | 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 | stomach cancer | sensitive | Akt Inhibitor (Pan) | Capivasertib | Preclinical - Cell culture | Actionable | In a preclinical study, a gastric cancer cell line harboring PIK3CA E545K was sensitive to treatment with Truqap (capivasertib), demonstrating decreased cell proliferation in culture (PMID: 32070411). | 32070411 |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) | Ipatasertib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Ipatasertib (GDC-0068) reduced tumor growth in a cell line xenograft model of hormone-receptor positive breast cancer harboring PIK3CA E545K (PMID: 32205017). | 32205017 |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) | Ipatasertib + Paclitaxel | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Ipatasertib (GDC-0068) and Taxol (paclitaxel) inhibited tumor growth in a cell line xenograft model of hormone-receptor positive breast cancer harboring PIK3CA E545K, and demonstrated increased activity over either agent alone (PMID: 32205017). | 32205017 |
| 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 | |
| PIK3CA E545K | ovarian cancer | predicted - sensitive | Akt Inhibitor (Pan) | TAS-117 | Case Reports/Case Series | Actionable | In a Phase II trial, TAS-117 treatment in an ovarian cancer patient harboring PIK3CA E545K led to a partial response at 6 weeks after treatment and a 39% decrease in tumor size, but subsequently progression was observed at 12 weeks in non-target lesions and an increase in tumor markers at 18 weeks, and TAS-117 treatment was discontinued (PMID: 33723724; NCT03017521). | 33723724 |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) | MK2206 | Preclinical - Cell culture | Actionable | In a preclinical study, MK2206 treatment inhibited Akt signaling, induced cell death, and inhibited proliferation of breast cancer cell lines harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) | ARQ 751 | Preclinical - Cell culture | Actionable | In a preclinical study, ARQ 751 treatment inhibited Akt signaling, induced cell death, and inhibited proliferation of breast cancer cell lines harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) | Miransertib | Preclinical - Cell culture | Actionable | In a preclinical study, Miransertib (ARQ092) treatment inhibited Akt signaling, induced cell death, and inhibited proliferation of breast cancer cell lines harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | GSK690693 | Preclinical - Cell culture | Actionable | In a preclinical study, GSK690693 treatment inhibited Akt signaling, induced cell death, and inhibited proliferation of breast cancer cell lines harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 | |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) | Ipatasertib | Preclinical - Cell culture | Actionable | In a preclinical study, Ipatasertib (GDC-0068) treatment inhibited Akt signaling, induced cell death, and inhibited proliferation of breast cancer cell lines harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) | AZD0156 + MK2206 | Preclinical - Cell culture | Actionable | In a preclinical study, AZD0156 and MK2206 combination treatment increased cell death compared to MK2206 alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) | ARQ 751 + AZD0156 | Preclinical - Cell culture | Actionable | In a preclinical study, AZD0156 and ARQ 751 combination treatment increased cell death compared to ARQ 751 alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) | AZD0156 + Miransertib | Preclinical - Cell culture | Actionable | In a preclinical study, AZD0156 and Miransertib (ARQ092) combination treatment increased cell death compared to Miransertib (ARQ092) alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | AZD0156 + GSK690693 | Preclinical - Cell culture | Actionable | In a preclinical study, AZD0156 and GSK690693 combination treatment increased cell death compared to GSK690693 alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 | |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) | AZD0156 + Ipatasertib | Preclinical - Cell culture | Actionable | In a preclinical study, AZD0156 and Ipatasertib (GDC-0068) combination treatment increased cell death compared to Ipatasertib (GDC-0068) alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) | Ipatasertib + KU-57788 | Preclinical - Cell culture | Actionable | In a preclinical study, KU-57788 and Ipatasertib (GDC-0068) combination treatment increased cell death compared to Ipatasertib (GDC-0068) alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) | KU-57788 + MK2206 | Preclinical - Cell culture | Actionable | In a preclinical study, KU-57788 and MK2206 combination treatment increased cell death compared to MK2206 alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) | ARQ 751 + KU-57788 | Preclinical - Cell culture | Actionable | In a preclinical study, KU-57788 and ARQ 751 combination treatment increased cell death compared to ARQ 751 alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) | KU-57788 + Miransertib | Preclinical - Cell culture | Actionable | In a preclinical study, KU-57788 and Miransertib (ARQ092) combination treatment increased cell death compared to Miransertib (ARQ092) alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | GSK690693 + KU-57788 | Preclinical - Cell culture | Actionable | In a preclinical study, KU-57788 and GSK690693 combination treatment increased cell death compared to GSK690693 alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 | |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) | GSK2334470 + MK2206 | Preclinical - Cell culture | Actionable | In a preclinical study, GSK2334470 and MK2206 combination treatment increased cell death compared to MK2206 alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) | ARQ 751 + GSK2334470 | Preclinical - Cell culture | Actionable | In a preclinical study, GSK2334470 and ARQ 751 combination treatment increased cell death compared to ARQ 751 alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | GSK2334470 + GSK690693 | Preclinical - Cell culture | Actionable | In a preclinical study, GSK2334470 and GSK690693 combination treatment increased cell death compared to GSK690693 alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 | |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) | GSK2334470 + Miransertib | Preclinical - Cell culture | Actionable | In a preclinical study, GSK2334470 and Miransertib (ARQ092) combination treatment increased cell death compared to Miransertib (ARQ092) alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) | GSK2334470 + Ipatasertib | Preclinical - Cell culture | Actionable | In a preclinical study, GSK2334470 and Ipatasertib (GDC0068) combination treatment increased cell death compared to Ipatasertib (GDC0068) alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) | Ipatasertib + OSU-T315 | Preclinical - Cell culture | Actionable | In a preclinical study, OSU-T315 and Ipatasertib (GDC0068) combination treatment increased cell death compared to Ipatasertib (GDC0068) alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) | MK2206 + OSU-T315 | Preclinical - Cell culture | Actionable | In a preclinical study, OSU-T315 and MK2206 combination treatment increased cell death compared to MK2206 alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) | ARQ 751 + OSU-T315 | Preclinical - Cell culture | Actionable | In a preclinical study, OSU-T315 and ARQ 751combination treatment increased cell death compared to ARQ 751 alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) | Miransertib + OSU-T315 | Preclinical - Cell culture | Actionable | In a preclinical study, OSU-T315 and Miransertib (ARQ092) combination treatment increased cell death compared to Miransertib (ARQ092) alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | GSK690693 + OSU-T315 | Preclinical - Cell culture | Actionable | In a preclinical study, OSU-T315 and GSK690693 combination treatment increased cell death compared to GSK690693 alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 | |
| PIK3CA E545K | breast cancer | decreased response | Akt Inhibitor (Pan) | ARQ 751 + LAM-002A | Preclinical - Cell culture | Actionable | In a preclinical study, LAM-002A (Apilimod dimesylate) and ARQ 751 combination treatment resulted in less cell death compared to ARQ 751 alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | decreased response | Akt Inhibitor (Pan) | LAM-002A + MK2206 | Preclinical - Cell culture | Actionable | In a preclinical study, LAM-002A (Apilimod dimesylate) and MK2206 combination treatment resulted in less cell death compared to MK2206 alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) mTORC1 Inhibitor | MK2206 + Sirolimus | Preclinical - Cell culture | Actionable | In a preclinical study, Rapamune (sirolimus) and MK2206 combination treatment increased cell death compared to MK2206 alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) mTORC1 Inhibitor | ARQ 751 + Sirolimus | Preclinical - Cell culture | Actionable | In a preclinical study, Rapamune (sirolimus) and ARQ 751 combination treatment increased cell death compared to ARQ 751 alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) mTORC1 Inhibitor | Miransertib + Sirolimus | Preclinical - Cell culture | Actionable | In a preclinical study, Rapamune (sirolimus) and Miransertib (ARQ092) combination treatment increased cell death compared to Miransertib (ARQ092) alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | mTORC1 Inhibitor | GSK690693 + Sirolimus | Preclinical - Cell culture | Actionable | In a preclinical study, Rapamune (sirolimus) and GSK690693 combination treatment increased cell death compared to GSK690693 alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) mTORC1 Inhibitor | Ipatasertib + Sirolimus | Preclinical - Cell culture | Actionable | In a preclinical study, Rapamune (sirolimus) and Ipatasertib (GDC0068) combination treatment increased cell death compared to Ipatasertib (GDC0068) alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) mTOR Inhibitor | MK2206 + Torin 1 | Preclinical - Cell culture | Actionable | In a preclinical study, Torin 1 and MK2206 combination treatment increased cell death compared to MK2206 alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) mTOR Inhibitor | ARQ 751 + Torin 1 | Preclinical - Cell culture | Actionable | In a preclinical study, Torin 1 and ARQ 751 combination treatment increased cell death compared to ARQ 751 alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) mTOR Inhibitor | Miransertib + Torin 1 | Preclinical - Cell culture | Actionable | In a preclinical study, Torin 1 and Miransertib (ARQ092) combination treatment increased cell death compared to Miransertib (ARQ092) alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | mTOR Inhibitor | GSK690693 + Torin 1 | Preclinical - Cell culture | Actionable | In a preclinical study, Torin 1 and GSK690693 combination treatment increased cell death compared to GSK690693 alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | breast cancer | sensitive | Akt Inhibitor (Pan) mTOR Inhibitor | Ipatasertib + Torin 1 | Preclinical - Cell culture | Actionable | In a preclinical study, Torin 1 and Ipatasertib (GDC0068) combination treatment increased cell death compared to Ipatasertib (GDC0068) alone in a breast cancer cell line harboring PIK3CA E545K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E545K | colon cancer | sensitive | PIK3CA inhibitor | Taselisib | Preclinical - Cell culture | Actionable | In a preclinical study, Taselisib (GDC-0032) treatment led to decreased cell viability in a colon cancer cell line expressing PIK3CA E545K in culture (PMID: 34544753). | 34544753 |
| PIK3CA E545K | colon cancer | no benefit | PI3K Inhibitor (Pan) | Pictilisib | Preclinical - Cell culture | Actionable | In a preclinical study, Pictilisib (GDC-0941) treatment did not affect cell viability in a colon cancer cell line expressing PIK3CA E545K in culture (PMID: 34544753). | 34544753 |
| PIK3CA E545K | colon cancer | sensitive | PIK3CA inhibitor | Inavolisib | Preclinical - Cell culture | Actionable | In a preclinical study, Inavolisib (GDC-0077) treatment led to decreased cell viability in a colon cancer cell line expressing PIK3CA E545K in culture (PMID: 34544753). | 34544753 |
| PIK3CA E545K | breast cancer | sensitive | PIK3CA inhibitor | Inavolisib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Inavolisib (GDC-0077) treatment led to tumor regression in an ESR1 (ER)-positive breast cancer cell line xenograft model harboring PIK3CA E545K (PMID: 34544753). | 34544753 |
| PIK3CA E545K | cervical cancer | predicted - sensitive | PIK3CA inhibitor | Alpelisib | Case Reports/Case Series | Actionable | In a Phase I trial, treatment with Piqray (alpelisib) resulted in an objective response rate of 33% (2/6; all partial responses), disease control rate of 100% (6/6), with stable disease in 5 patients, in cervical cancer patients harboring PIK3CA mutations, including PIK3CA E545K (PMID: 35311394). | 35311394 |
| PIK3CA E545K | breast cancer | sensitive | mTORC1 Inhibitor | Sirolimus | Preclinical - Cell culture | Actionable | In a preclinical study, a breast cancer cell line harboring PIK3CA E545K demonstrated hypersensitivity to Rapamune (sirolimus)-induced growth inhibition in culture (PMID: 24631838). | 24631838 |
| PIK3CA E545K | estrogen-receptor positive breast cancer | predicted - sensitive | mTORC1 Inhibitor PIK3CA inhibitor | Alpelisib + Everolimus | Preclinical - Patient cell culture | Actionable | In a preclinical study, combination treatment with Piqray (albelisib) and Afinitor (everolimus) inhibited cell viability of patient-derived ESR1 (ER)-positive breast cancer cells harboring PIK3CA E545K in culture (PMID: 36900375). | 36900375 |
| PIK3CA E545K | estrogen-receptor positive breast cancer | predicted - sensitive | PIK3CA inhibitor | Afatinib + Alpelisib | Preclinical - Patient cell culture | Actionable | In a preclinical study, combination treatment with Piqray (albelisib) and Gilotrif (afatinib) synergistically inhibited cell viability of patient-derived ESR1 (ER)-positive breast cancer cells harboring PIK3CA E545K in culture (PMID: 36900375). | 36900375 |
| PIK3CA E545K | diffuse midline glioma, H3 K27M-mutant | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of mouse glioma cells expressing H3.1 K28M (reported as H3.1 K27M), ACVR1 G328V, and PIK3CA E545K in culture (PMID: 37011011). | 37011011 | |
| PIK3CA E545K | urinary bladder cancer | sensitive | Akt Inhibitor (Pan) | MK2206 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, MK2206 increased apoptosis and inhibited viability in bladder cancer cell lines harboring PIK3CA E545K in culture and inhibited tumor growth in cell line xenograft models (PMID: 25349966). | 25349966 |
| PIK3CA E545K | clear cell adenocarcinoma | predicted - sensitive | PIK3CA inhibitor | Copanlisib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI MATCH EAY131-Z1F), Aliqopa (copanlisib) treatment resulted in a partial response and progression-free survival of 7.3 months and an overall survival of 19.8 months in a patient with clear cell carcinoma of anterior abdominal wall harboring PIK3CA E545K (PMID: 35133871; NCT02465060). | 35133871 |
| PIK3CA E545K | cervical cancer | predicted - sensitive | Pembrolizumab | Case Reports/Case Series | Actionable | In a clinical case study, Keytruda (pembrolizumab) treatment resulted in complete remission in a patient with metastatic cervical cancer harboring PIK3CA E545K and moderate tumor mutational burden (TMB) (9.2 mut/Mb) (PMID: 37469254). | 37469254 | |
| PIK3CA E545K | cervical cancer | predicted - sensitive | PIK3CA inhibitor | Alpelisib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Piqray (alpelisib) increased apoptosis and decreased colony formation in a cervical cancer cell line harboring PIK3CA E545K in culture and decreased tumor cell proliferation and increased CD8-positive T-cell differentiation and proliferation in a cell line xenograft model (PMID: 37469254). | 37469254 |
| PIK3CA E545K | cervical cancer | sensitive | PIK3CA inhibitor | Alpelisib + Toripalimab-tpzi | Preclinical - Pdx | Actionable | In a preclinical study, the combination of Piqray (alpelisib) and Loqtorz (toripalimab-tpzi) inhibited proliferation in cell line xenograft models of cervical cancer harboring PIK3CA E545K and in a patient-derived xenograft (PDX) model (PMID: 37469254). | 37469254 |
| PIK3CA E545K | head and neck squamous cell carcinoma | sensitive | PIK3CA inhibitor | Alpelisib + Tipifarnib | Preclinical - Pdx | Actionable | In a preclinical study, the combination of Piqray (alpelisib) and Zarnestra (tipifarnib) inhibited tumor growth in a patient-derived xenograft (PDX) model of head and neck squamous cell carcinoma harboring PIK3CA E545K (PMID: 37339176). | 37339176 |
| PIK3CA E545K | stomach cancer | sensitive | PIK3CA inhibitor | Alpelisib | Preclinical - Cell culture | Actionable | In a preclinical study, Piqray (alpelisib) inhibited growth and induced cell cycle arrest and inhibited phosphorylation of Akt and S6 in a gastric cancer cell line harboring PIK3CA E545K in culture (PMID: 37493631). | 37493631 |
| PIK3CA E545K | stomach cancer | sensitive | PIK3CA inhibitor | A-1331852 + Alpelisib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Piqray (alpelisib) and A-1331852 synergistically inhibited viability in a gastric cancer cell line harboring PIK3CA E545K in culture (PMID: 37493631). | 37493631 |
| PIK3CA E545K | head and neck squamous cell carcinoma | sensitive | PIK3CA inhibitor | STX-478 | Preclinical - Pdx | Actionable | In a preclinical study, STX-478 inhibited tumor growth of a head and neck squamous cell cancer patient-derived xenograft (PDX) model harboring PIK3CA E545K (PMID: 37623743). | 37623743 |
| PIK3CA E545K | Her2-receptor negative breast cancer | predicted - sensitive | PIK3CA inhibitor | HS-10352 | Case Reports/Case Series | Actionable | In a Phase I trial, HS-10352 treatment resulted in an objective response rate (ORR) of 27.8% (5/18, all partial responses), disease control rate (DCR) of 55.6%, and median progression-free survival (mPFS) of 3.9 mo in HR-positive, ERBB2 (HER2)-negative advanced breast cancer patients overall, and in the 6mg group led to an ORR of 66.7% and DCR of 83.3%, with an ORR of 75.0% (3/4) and DCR of 100% in patients with PIK3CA mutations (E542K, E545K, E545D, H1047L, H1047R) (PMID: 38037839; NCT04631835). | 38037839 |
| PIK3CA E545K | breast cancer | sensitive | PIK3CA inhibitor | RLY-2608 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, RLY-2608 inhibited proliferation of hormone receptor-positive breast cancer cells harboring PIK3CA E545K in culture, and led to tumor regression in a cell line xenograft model (PMID: 37916956). | 37916956 |