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| Profile Name | PIK3CA E542K |
| 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 E542K | colon adenocarcinoma | sensitive | mTOR Inhibitor PI3K Inhibitor (Pan) | 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 | colorectal cancer | sensitive | PI3K Inhibitor (Pan) | 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 | 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 E542K mutations (PMID: 15647370). | 15647370 |
| PIK3CA E542K | gastrointestinal system cancer | sensitive | Akt Inhibitor (Pan) | Capivasertib | Preclinical - Cell culture | Actionable | In a preclinical study, gastric cancer cells harboring PIK3CA E542K demonstrated sensitivity to the AKT inhibitor Truqap (capivasertib), resulting in decreased proliferation in culture (PMID: 24088382). | 24088382 |
| PIK3CA E542K | breast cancer | sensitive | PI3K Inhibitor (Pan) | MEN1611 | Preclinical | Actionable | In a preclinical study, MEN1611 (CH5132799) inhibited proliferation of a breast cancer cell line harboring PIK3CA E542K in culture (PMID: 21558396). | 21558396 |
| 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 | 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 E542K in culture (PMID: 26627007). | 26627007 |
| PIK3CA E542K | 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 E542K in culture (PMID: 26627007). | 26627007 |
| PIK3CA E542K | breast cancer | sensitive | Akt Inhibitor (Pan) | 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 | 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 | 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 | 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 | 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 a partial response in a patient with head and neck squamous cell carcinoma harboring a PIK3CA E542K mutation (PMID: 26787751; NCT00854152). | 26787751 |
| PIK3CA E542K | papillary thyroid carcinoma | sensitive | Akt Inhibitor (Pan) | 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 | papillary thyroid carcinoma | sensitive | Akt Inhibitor (Pan) mTORC1 Inhibitor | 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 | breast cancer | sensitive | Akt Inhibitor (Pan) | 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 | 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 | cervical squamous cell carcinoma | sensitive | Akt Inhibitor (Pan) | 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 | breast cancer | resistant | PI3K Inhibitor (Pan) | 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 | 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 no responses in patients harboring PIK3CA E542K (n=6) (PMID: 31158500; NCT02785913). | 31158500 |
| PIK3CA E542K | 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 E542K | endometrial adenocarcinoma | no benefit | PIK3CA inhibitor | 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 | high grade glioma | sensitive | PI3K Inhibitor (Pan) | 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 | stomach cancer | sensitive | Akt Inhibitor (Pan) | Capivasertib | Case Reports/Case Series | Actionable | In a clinical case study, treatment with Truqap (capivasertib) 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 | head and neck squamous cell carcinoma | predicted - sensitive | PIK3CA inhibitor | 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 E542K 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 | stomach cancer | sensitive | Akt Inhibitor (Pan) | MK2206 | Preclinical - Cell culture | Actionable | In a preclinical study, MK2206 treatment induced cell death and inhibited proliferation of a gastric cancer cell line harboring PIK3CA E542K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E542K | stomach cancer | sensitive | Akt Inhibitor (Pan) | ARQ 751 | Preclinical - Cell culture | Actionable | In a preclinical study, ARQ 751 treatment induced cell death and inhibited proliferation of a gastric cancer cell line harboring PIK3CA E542K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E542K | stomach cancer | sensitive | Akt Inhibitor (Pan) | Miransertib | Preclinical - Cell culture | Actionable | In a preclinical study, Miransertib (ARQ092) treatment induced cell death and inhibited proliferation of a gastric cancer cell line harboring PIK3CA E542K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E542K | stomach cancer | predicted - sensitive | GSK690693 | Preclinical - Cell culture | Actionable | In a preclinical study, GSK690693 treatment did not increase cell death but inhibited proliferation of a gastric cancer cell line harboring PIK3CA E542K in culture (PMID: 32439931). | 32439931 | |
| PIK3CA E542K | stomach cancer | predicted - sensitive | Akt Inhibitor (Pan) | Ipatasertib | Preclinical - Cell culture | Actionable | In a preclinical study, Ipatasertib (GDC-0068) treatment did not increase cell death but inhibited proliferation of a gastric cancer cell line harboring PIK3CA E542K in culture (PMID: 32439931). | 32439931 |
| PIK3CA E542K | endometrial serous 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 5.4 months and an overall survival of 8.2 months in a patient with endometrial serous adenocarcinoma harboring PIK3CA E542K (PMID: 35133871; NCT02465060). | 35133871 |
| PIK3CA E542K | Her2-receptor positive breast cancer | sensitive | PIK3CA inhibitor | STX-478 | Preclinical - Pdx | Actionable | In a preclinical study, STX-478 inhibited tumor growth of a ERBB2 (HER2)-positive breast cancer patient-derived xenograft (PDX) model harboring PIK3CA E542K (PMID: 37623743). | 37623743 |
| PIK3CA E542K | 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 E542K | estrogen-receptor positive breast cancer | predicted - sensitive | PIK3CA inhibitor | RLY-2608 | Case Reports/Case Series | Actionable | In a clinical case study, treatment with RLY-2608 resulted in a partial response with disappearance of the soft tissue target lesion, which was ongoing at day 141, in a patient with ESR1/PGR-positive, ERBB2 (HER2)-negative breast cancer harboring PIK3CA E542K (PMID: 37916956; NCT05216432). | 37916956 |
| PIK3CA E542K | lung squamous cell carcinoma | sensitive | PI3K Inhibitor (Pan) | Buparlisib + Carboplatin + Paclitaxel | Preclinical - Pdx | Actionable | In a preclinical study, the addition of Buparlisib (BKM120) to treatment with the combination of Paraplatin (carboplatin) and Taxol (paclitaxel) resulted in improved tumor growth inhibition compared to chemotherapy or Buparlisib (BKM120) alone in a patient-derived xenograft (PDX) model of squamous non-small cell lung cancer harboring PIK3CA E542K and CDKN2A S12* (PMID: 39199558). | 39199558 |