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Gene | PIK3CA |
Variant | amp |
Impact List | none |
Protein Effect | no effect |
Gene Variant Descriptions | PIK3CA amplification indicates an increased number of copies of the PIK3CA gene. However, the mechanism causing the increase is unspecified. |
Associated Drug Resistance |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
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 | 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 | 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 | 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 | 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 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 | 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 | 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 | 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 | 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 | 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 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 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 |
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 |
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 |
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 |
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 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 |
Molecular Profile | Protein Effect | Treatment Approaches |
---|---|---|
PIK3CA amp | no effect | |
PIK3CA E545K PIK3CA amp | ||
PIK3CA E542K PIK3CA amp | ||
CDKN2A loss PIK3CA E545K PIK3CA amp | ||
CDKN2A loss PIK3CA E542K PIK3CA amp | ||
ERBB2 pos PIK3CA amp |