Gene Variant Detail

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Gene PIK3CA
Variant E542K
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions PIK3CA E542K is a hotspot mutation that lies within the PIK helical domain of the Pik3ca protein (UniProt.org). E542K results in increased phosphorylation of Akt, growth factor-independent cell survival, and is transforming in cell culture (PMID: 16533766, PMID: 26627007, PMID: 29533785).
Associated Drug Resistance

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Transcript NM_006218
gDNA chr3:g.179218294G>A
cDNA c.1624G>A
Protein p.E542K
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
XM_006713658 chr3:g.179218294G>A c.1624G>A p.E542K RefSeq GRCh38/hg38
XM_011512894 chr3:g.179218294G>A c.1624G>A p.E542K RefSeq GRCh38/hg38
NM_006218 chr3:g.179218294G>A c.1624G>A p.E542K RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 BEZ235 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 malignant glioma sensitive Buparlisib + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Buparlisib (BKM120) and Selumetinib (AZD6244) 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 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 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 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 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 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 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 Selumetinib (AZD6244) 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