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Gene | PIK3CA |
Variant | H1047R |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | PIK3CA H1047R is a hotspot mutation that lies within the kinase domain of the Pik3ca protein (UniProt.org). H1047R results in increased phosphorylation of Akt and Mek1/2, growth factor-independent cell survival, and transformation in cell culture (PMID: 26627007, PMID: 29533785). |
Associated Drug Resistance | |
Category Variants Paths |
PIK3CA mutant PIK3CA act mut PIK3CA H1047R PIK3CA mutant PIK3CA exon21 PIK3CA H1047X PIK3CA H1047R |
Transcript | NM_006218.4 |
gDNA | chr3:g.179234297A>G |
cDNA | c.3140A>G |
Protein | p.H1047R |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_006218 | chr3:g.179234297A>G | c.3140A>G | p.H1047R | RefSeq | GRCh38/hg38 |
NM_006218.3 | chr3:g.179234297A>G | c.3140A>G | p.H1047R | RefSeq | GRCh38/hg38 |
XM_006713658.5 | chr3:g.179234297A>G | c.3140A>G | p.H1047R | RefSeq | GRCh38/hg38 |
NM_006218.4 | chr3:g.179234297A>G | c.3140A>G | p.H1047R | RefSeq | GRCh38/hg38 |
XM_011512894 | chr3:g.179234297A>G | c.3140A>G | p.H1047R | RefSeq | GRCh38/hg38 |
XM_006713658 | chr3:g.179234297A>G | c.3140A>G | p.H1047R | RefSeq | GRCh38/hg38 |
XM_006713658.4 | chr3:g.179234297A>G | c.3140A>G | p.H1047R | RefSeq | GRCh38/hg38 |
XM_011512894.2 | chr3:g.179234297A>G | c.3140A>G | p.H1047R | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
PIK3CA H1047R | lung adenocarcinoma | sensitive | Dactolisib | Preclinical | Actionable | In a preclinical study, BEZ235 promoted tumor regression in a mouse lung adenocarcinoma model expressing PIK3CA H1047R (PMID: 19029981). | 19029981 |
PIK3CA H1047R | lung adenocarcinoma | no benefit | Sirolimus | Preclinical | Actionable | In a preclinical study, Sirolimus (rapamycin) failed to inhibit tumor growth in a mouse lung adenocarcinoma model expressing the PIK3CA H1047R mutation (PMID: 19029981). | 19029981 |
PIK3CA H1047R | lung cancer | sensitive | Dactolisib | Preclinical | Actionable | In a preclinical study, BEZ235 reduced tumor size in mouse models of lung cancer carrying PIK3CA H1047R (PMID: 19029981). | 19029981 |
PIK3CA H1047R | lung cancer | no benefit | Sirolimus | Preclinical | Actionable | In a preclinical study, Sirolimus (rapamycin) did not induce tumor shrinkage in mouse lung cancer models carrying PIK3CA H1047R (PMID: 19029981). | 19029981 |
PIK3CA H1047R | ovarian cancer | sensitive | PF-04691502 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PF-04691502 inhibited Pi3k signaling, resulted in growth inhibition of ovarian cancer cells harboring PIK3CA H1047R in culture and in cell line xenograft models (PMID: 21750219). | 21750219 |
PIK3CA H1047R | Advanced Solid Tumor | sensitive | A66 | Preclinical | Actionable | In a preclinical study, A66 delayed tumor growth in human tumor xenograft models harboring PIK3CA H1047R mutations (PMID: 21668414). | 21668414 |
PIK3CA H1047R | stomach cancer | sensitive | Capivasertib | Preclinical - Pdx | Actionable | In a preclinical study, Truqap (capivasertib) inhibited growth in a patient-derived xenograft model of gastric cancer harboring a PIK3CA H1047R mutation (PMID: 24088382). | 24088382 |
PIK3CA H1047R | ovarian cancer | predicted - sensitive | MEN1611 | Case Reports/Case Series | Actionable | In a Phase I trial, MEN1611 (CH5132799) demonstrated safety and preliminary efficacy in patients with advanced solid tumors, including a partial response in a patient with ovarian cancer harboring PIK3CA H1047R (PMID: 25231405). | 25231405 |
PIK3CA H1047R | breast cancer | sensitive | MEN1611 | Preclinical | Actionable | In a preclinical study, MEN1611 (CH5132799) inhibited proliferation of breast cancer cells harboring PIK3CA H1047R in culture (PMID: 21558396). | 21558396 |
PIK3CA H1047R | breast cancer | sensitive | MEN1611 | Preclinical - Cell culture | Actionable | In a preclinical study, MEN1611 (CH5132799) inhibited viability and induced degradation of p110alpha in breast cancer cell lines harboring PIK3CA H1047R in culture (PMID: 36913051). | 36913051 |
PIK3CA H1047R | breast cancer | sensitive | Gedatolisib | Preclinical | Actionable | In a preclinical study, Gedatolisib (PKI-587) inhibited growth of human breast cancer cells harboring PIK3CA H1047R in culture (PMID: 21325073, PMID: 17314276). | 17314276 21325073 |
PIK3CA H1047R | ovarian cancer | sensitive | AZD8835 | Preclinical | Actionable | In a preclinical study, AZD8835 inhibited tumor growth in mouse xenografts of ovarian cancer with a Pik3ca H1047R mutation (AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2830). | detail... |
PIK3CA H1047R | colorectal cancer | sensitive | Cetuximab | Case Reports/Case Series | Actionable | In a retrospective analysis, Erbitux (cetuximab) combined with radiation therapy resulted in stable disease for 6 months in a colorectal carcinoma patient harboring a PIK3CA H1047R mutation (PMID: 25714871). | 25714871 |
PIK3CA H1047R | breast cancer | sensitive | Dactolisib | Preclinical | Actionable | In a preclinical study, BEZ235 inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA H1047R in culture (PMID: 26627007). | 26627007 |
PIK3CA H1047R | breast cancer | sensitive | Alpelisib | Preclinical | Actionable | In a preclinical study, Alpelisib (BYL719) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA H1047R in culture (PMID: 26627007). | 26627007 |
PIK3CA H1047R | breast cancer | sensitive | Alpelisib | Preclinical - Cell culture | Actionable | In a preclinical study, Piqray (alpelisib) inhibited growth of breast cancer organoids harboring PIK3CA H1047R in culture (PMID: 37272756). | 37272756 |
PIK3CA H1047R | breast cancer | sensitive | MK2206 | Preclinical - Cell culture | Actionable | In a preclinical study, MK2206 inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA H1047R in culture (PMID: 26627007). | 26627007 |
PIK3CA H1047R | breast cancer | sensitive | MK2206 | Preclinical - Cell culture | Actionable | In a preclinical study, MK2206 treatment did not increase cell death but inhibited proliferation of breast cancer cells harboring PIK3CA H1047R in culture (PMID: 32439931). | 32439931 |
PIK3CA H1047R | breast cancer | sensitive | Lapatinib | Preclinical | Actionable | In a preclinical study, Tykerb (lapatinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA H1047R in culture (PMID: 26627007). | 26627007 |
PIK3CA H1047R | breast cancer | sensitive | Neratinib | Preclinical - Cell culture | Actionable | In a preclinical study, Nerlynx (neratinib) inhibited growth of breast cancer organoids harboring PIK3CA H1047R in culture (PMID: 37272756). | 37272756 |
PIK3CA H1047R | breast cancer | sensitive | Neratinib | Preclinical | Actionable | In a preclinical study, Nerlynx (neratinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA H1047R in culture (PMID: 26627007). | 26627007 |
PIK3CA H1047R | breast cancer | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA H1047R in culture (PMID: 26627007). | 26627007 |
PIK3CA H1047R | Advanced Solid Tumor | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited survival of transformed cell lines overexpressing PIK3CA H1047R in culture (PMID: 26627007). | 26627007 |
PIK3CA H1047R | head and neck squamous cell carcinoma | sensitive | Sirolimus + Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Rapamune (sirolimus) worked synergistically with Mekinist (trametinib) to inhibit proliferation of head and neck squamous carcinoma cell lines harboring PIK3CA H1047R in culture and to reduce tumor growth in cell line xenograft models (PMID: 26882569). | 26882569 |
PIK3CA H1047R | head and neck squamous cell carcinoma | sensitive | Radiotherapy + Taselisib | Preclinical | Actionable | In a preclinical study, Taselisib (GDC-0032) enhanced the effects of radiation induced apoptosis of head and neck squamous carcinoma cells harboring PIK3CA H1047R (PMID: 26589432). | 26589432 |
PIK3CA H1047R | Advanced Solid Tumor | sensitive | Sirolimus | Preclinical | Actionable | In a preclinical study, transformed cells expressing PIK3CA H1047R were sensitive to Rapamune (sirolimus), resulting in inhibition of transformation in culture (PMID: 15647370). | 15647370 |
PIK3CA H1047R | urinary bladder cancer | sensitive | Dactolisib | Preclinical - Pdx | Actionable | In a preclinical study, BEZ235 inhibited tumor growth in a patient-derived xenograft (PDX) model of bladder cancer harboring PIK3CA H1047R (PMID: 26270481). | 26270481 |
PIK3CA H1047R | ovarian cancer | sensitive | A66 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, A66 delayed tumor growth in an ovarian cancer cell line xenograft model harboring PIK3CA H1047R (PMID: 21668414). | 21668414 |
PIK3CA H1047R | lung squamous cell carcinoma | sensitive | 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 expressing PIK3CA H1047R in culture (PMID: 26013318). | 26013318 |
PIK3CA H1047R | lung squamous cell carcinoma | sensitive | 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 H1047R in culture (PMID: 26013318). | 26013318 |
PIK3CA H1047R | lung squamous cell carcinoma | sensitive | 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 H1047R in culture (PMID: 26013318). | 26013318 |
PIK3CA H1047R | thyroid cancer | 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 an anaplastic thyroid cancer cell line harboring PIK3CA H1047R (PMID: 21289267). | 21289267 |
PIK3CA H1047R | thyroid cancer | sensitive | MK2206 + Temsirolimus | Preclinical - Cell culture | Actionable | In a preclinical study, MK2206 and Torisel (temsirolimus) demonstrated synergy in inhibiting growth of an anaplastic thyroid cancer cell line harboring PIK3CA H1047R in culture (PMID: 21289267). | 21289267 |
PIK3CA H1047R | head and neck squamous cell carcinoma | sensitive | Gedatolisib | Preclinical - Cell culture | Actionable | In a preclinical study, head and neck squamous cell carcinoma cell lines harboring PIK3CA H1047R demonstrated sensitivity to treatment with Gedatolisib (PF-05212384) in culture (PMID: 25977343). | 25977343 |
PIK3CA H1047R | Advanced Solid Tumor | sensitive | Rigosertib Sodium | Preclinical - Cell culture | Actionable | In a preclinical study, Rigosertib (ON 01910.Na) inhibited oncogenic transformation in fibroblast cells over-expressing Pik3ca H1047R in culture (PMID: 27104980). | 27104980 |
PIK3CA H1047R | breast cancer | sensitive | BAY1125976 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, BAY1125976 inhibited proliferation of breast cancer cell lines harboring PIK3CA H1047R in culture, and inhibited AKT signaling and tumor growth in a PIK3CA H1047R-mutant cell line xenograft model (PMID: 27699769). | 27699769 |
PIK3CA H1047R | breast cancer | sensitive | Metformin | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Glucophage (metformin) inhibited cell proliferation of a dietary restriction-resistant PIK3CA H1047R-harboring human breast cancer cell line in culture, and inhibited tumor growth in xenograft models (PMID: 23986086). | 23986086 |
PIK3CA H1047R | colorectal cancer | sensitive | Metformin | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Glucophage (metformin) demonstrated efficacy in treating dietary restriction-resistant human colorectal cancer cell line xenograft tumors harboring PIK3CA H1047R (PMID: 23986086). | 23986086 |
PIK3CA H1047R | breast cancer | sensitive | Miransertib | Preclinical - Cell culture | Actionable | In a preclinical study, a breast cancer cell line harboring PIK3CA H1047R demonstrated sensitivity to treatment with Miransertib (ARQ092) in culture, resulting in inhibition of cell proliferation (PMID: 26469692). | 26469692 |
PIK3CA H1047R | breast cancer | sensitive | Miransertib | Preclinical - Cell culture | Actionable | In a preclinical study, Miransertib (ARQ092) treatment did not increase cell death but inhibited proliferation of breast cancer cells harboring PIK3CA H1047R in culture (PMID: 32439931). | 32439931 |
PIK3CA H1047R | breast cancer | sensitive | ARQ 751 | Preclinical - Cell culture | Actionable | In a preclinical study, a breast cancer cell line harboring PIK3CA H1047R demonstrated sensitivity to treatment with ARQ 751 in culture, resulting in inhibition of cell proliferation (PMID: 26469692). | 26469692 |
PIK3CA H1047R | breast cancer | sensitive | ARQ 751 | Preclinical - Cell culture | Actionable | In a preclinical study, ARQ 751 treatment did not increase cell death but inhibited proliferation of breast cancer cells harboring PIK3CA H1047R in culture (PMID: 32439931). | 32439931 |
PIK3CA H1047R | breast cancer | sensitive | M2698 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a breast cancer xenograft model harboring PIK3CA H1047R was sensitive to M2698 (MSC2363318A), demonstrating inhibition of tumor growth (PMID: 27186432). | 27186432 |
PIK3CA H1047R | breast cancer | sensitive | DHM25 | Preclinical - Cell culture | Actionable | In a preclinical study, DHM25 increased cell death in breast cancer cell lines harboring PIK3CA H1047R in culture (PMID: 26237138). | 26237138 |
PIK3CA H1047R | breast cancer | sensitive | Taselisib | Phase I | Actionable | In a Phase I trial, four patients with breast cancer harboring PIK3CA H1047R demonstrated a confirmed partial response when treated with Taselisib (GDC-0032) (PMID: 28331003). | 28331003 |
PIK3CA H1047R | breast cancer | sensitive | Buparlisib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a breast cancer cell line xenograft model harboring PIK3CA H1047R demonstrated tumor regression within the mammary fat pad when treated with Buparlisib (BKM120) (PMID: 28539475). | 28539475 |
PIK3CA H1047R | colorectal cancer | resistant | Cetuximab + Fluorouracil | Preclinical - Cell culture | Actionable | In a preclinical study, colorectal cancer cells over expressing PIK3CA H1047R were resistant to Erbitux (cetuximab) and Fluorouracil combination treatment in culture (PMID: 28424201). | 28424201 |
PIK3CA H1047R | urinary bladder cancer | sensitive | Pictilisib | Preclinical - Pdx | Actionable | In a preclinical study, Pictilisib (GDC-0941) inhibited Akt phosphorylation and tumor growth, prolonged survival in patient-derived xenograft (PDX) models of bladder cancer harboring PIK3CA H1047R (PMID: 28808038). | 28808038 |
PIK3CA H1047R | urinary bladder cancer | sensitive | Cisplatin + Pictilisib | Preclinical - Pdx | Actionable | In a preclinical study, combination of or sequential treatment with Pictilisib (GDC-0941) and Platinol (cisplatin) significantly delayed tumor growth and prolonged survival in patient-derived xenograft (PDX) models of bladder cancer harboring PIK3CA H1047R (PMID: 28808038). | 28808038 |
PIK3CA H1047R | breast metaplastic carcinoma | predicted - sensitive | Buparlisib + Paclitaxel | Case Reports/Case Series | Actionable | In a clinical case study, Buparlisib (BKM120) in combination with Taxol (paclitaxel) resulted in a durable partial response in a patient with breast metaplastic carcinoma harboring PIK3CA H1047R, with a total response period of 70 weeks and an overall survival of 42 months (PMID: 30577988). | 30577988 |
PIK3CA H1047R | 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, resulting in no responses in patients harboring PIK3CA H1047R (n=4) (PMID: 31158500; NCT02785913). | 31158500 |
PIK3CA H1047R | estrogen-receptor positive breast cancer | predicted - sensitive | Everolimus | Clinical Study - Cohort | Actionable | In a retrospective analysis, combination of Afinitor (everolimus) and hormone therapy resulted in improved median progression-free survival (8.8 vs 4.1 months, p=0.02) in patients with hormone receptor-positive metastatic breast cancer harboring PIK3CA H1047R (n=6) compared to patients without PIK3CA H1047R (n=10) (PMID: 31088410). | 31088410 |
PIK3CA H1047R | progesterone-receptor positive breast cancer | predicted - sensitive | Everolimus | Clinical Study - Cohort | Actionable | In a retrospective analysis, combination of Afinitor (everolimus) and hormone therapy resulted in improved median progression-free survival (8.8 vs 4.1 months, p=0.02) in patients with hormone receptor-positive metastatic breast cancer harboring PIK3CA H1047R (n=6) compared to patients without PIK3CA H1047R (n=10) (PMID: 31088410). | 31088410 |
PIK3CA H1047R | head and neck squamous cell carcinoma | predicted - sensitive | SHR-A1307 | Preclinical - Cell culture | Actionable | In a preclinical study, head and neck squamous cell carcinoma cells harboring PIK3CA H1047R treated with SHR-A1307 demonstrated inhibition of cell growth in culture (PMID: 30962319). | 30962319 |
PIK3CA H1047R | head and neck squamous cell carcinoma | resistant | Cetuximab | Preclinical - Cell culture | Actionable | In a preclinical study, head and neck squamous cell carcinoma cells harboring PIK3CA H1047R were resistant to Erbitux (cetuximab) in culture (PMID: 30962319). | 30962319 |
PIK3CA H1047R | Advanced Solid Tumor | predicted - sensitive | Alpelisib | Preclinical - Cell culture | Actionable | In a preclinical study, Piqray (Alpelisib) decreased Akt phosphorylation and inhibited PI3K signaling, and demonstrated dose-dependent inhibition of survival in human pluripotent stem cells harboring PIK3CA H1047R in culture (PMID: 30948643). | 30948643 |
PIK3CA H1047R | breast cancer | sensitive | CYH33 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, CYH33 inhibited proliferation of breast cancer cell lines harboring PIK3CA H1047R in culture, inhibited tumor progression in a transgenic mouse model, and induced cell cycle arrest, and inhibited PI3K signaling and tumor growth in cell line xenograft models (PMID: 30003928). | 30003928 |
PIK3CA H1047R | 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 H1047R | breast cancer | sensitive | Borussertib | Preclinical - Cell culture | Actionable | In a preclinical study, borussertib inhibited proliferation of a breast cancer cell line harboring PIK3CA H1047R in culture (PMID: 30858154). | 30858154 |
PIK3CA H1047R | high grade glioma | sensitive | 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 growth inhibition of astrocytoma cells expressing PIK3CA H1047R, but did not result in an effect as high as that seen in cells expressing PIK3CA R88Q or PIK3CA E542K in culture (PMID: 29975751). | 29975751 |
PIK3CA H1047R | head and neck squamous cell carcinoma | predicted - sensitive | Sulindac | Preclinical - Cell culture | Actionable | In a preclinical study, head and neck squamous cell carcinoma cell lines harboring PIK3CA H1047R demonstrated increased sensitivity to Clinoril (sulindac) compared to cell lines with wild-type PIK3CA, resulting in decreased proliferation in culture (PMID: 30683736). | 30683736 |
PIK3CA H1047R | oral squamous cell carcinoma | resistant | Palbociclib | Preclinical - Cell culture | Actionable | In a preclinical study, oral squamous cell carcinoma cells expressing PIK3CA H1047R demonstrated resistance to Ibrance (palbociclib) treatment in culture (PMID: 31516747). | 31516747 |
PIK3CA H1047R | oral squamous cell carcinoma | decreased response | Ribociclib | Preclinical - Cell culture | Actionable | In a preclinical study, oral squamous cell carcinoma cells expressing PIK3CA H1047R demonstrated reduced sensitivity to Kisqali (ribociclib) treatment compared to cells expressing wild-type PIK3CA in culture (PMID: 31516747). | 31516747 |
PIK3CA H1047R | oral squamous cell carcinoma | decreased response | Abemaciclib | Preclinical - Cell culture | Actionable | In a preclinical study, oral squamous cell carcinoma cells expressing PIK3CA H1047R demonstrated reduced sensitivity to Verzenio (abemaciclib) treatment compared to cells expressing wild-type PIK3CA in culture (PMID: 31516747). | 31516747 |
PIK3CA H1047R | transitional cell carcinoma | no benefit | Buparlisib | Case Reports/Case Series | Actionable | In a Phase II trial, Buparlisib (BKM120) treatment resulted in progressive disease in a patient with metastatic urothelial carcinoma harboring PIK3CA H1047R (PMID: 32767682; NCT01551030). | 32767682 |
PIK3CA H1047R | colon cancer | sensitive | T-2143 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, T-2143 treatment inhibited Akt phosphorylation and proliferation of colon cancer cells harboring PIK3CA H1047R in culture, and inhibited tumor growth in a cell line xenograft model (PMID: 32499300). | 32499300 |
PIK3CA H1047R | breast cancer | predicted - sensitive | TAS-117 | Case Reports/Case Series | Actionable | In a Phase II trial, TAS-117 treatment in a breast cancer patient harboring PIK3CA H1047R led to initial stable disease, however, disease progression was observed at 12 weeks after treatment along with an increase of non-target lesions, following which treatment was discontinued (PMID: 33723724; NCT03017521). | 33723724 |
PIK3CA H1047R | breast cancer | predicted - sensitive | GSK690693 | Preclinical - Cell culture | Actionable | In a preclinical study, GSK690693 treatment did not increase cell death but inhibited proliferation of breast cancer cells harboring PIK3CA H1047R in culture (PMID: 32439931). | 32439931 |
PIK3CA H1047R | breast cancer | predicted - sensitive | Ipatasertib | Preclinical - Cell culture | Actionable | In a preclinical study, Ipatasertib (GDC-0068) treatment did not increase cell death but inhibited proliferation of breast cancer cells harboring PIK3CA H1047R in culture (PMID: 32439931). | 32439931 |
PIK3CA H1047R | colon cancer | sensitive | 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 H1047R in culture (PMID: 34544753). | 34544753 |
PIK3CA H1047R | colon cancer | no benefit | 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 H1047R in culture (PMID: 34544753). | 34544753 |
PIK3CA H1047R | colon cancer | sensitive | Inavolisib | Preclinical - Cell culture | Actionable | In a preclinical study, Itovebi (inavolisib) treatment led to decreased cell viability in a colon cancer cell line expressing PIK3CA H1047R in culture (PMID: 34544753). | 34544753 |
PIK3CA H1047R | breast cancer | predicted - sensitive | LOXO-783 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, LOXO-783 (LOX-22783) treatment led to growth inhibition in breast cancer cell lines harboring PIK3CA H1047R, and led to tumor regression in cell line xenograft and patient-derived xenograft (PDX) models (Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P142). | detail... |
PIK3CA H1047R | colon cancer | sensitive | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Koselugo (selumetinib) inhibited viability of a colon cancer cell line expressing PIK3CA H1047R in culture (PMID: 27636997). | 27636997 |
PIK3CA H1047R | colon cancer | sensitive | Pimasertib | Preclinical - Cell culture | Actionable | In a preclinical study, Pimasertib (MSC1936369B) inhibited viability of a colon cancer cell line expressing PIK3CA H1047R in culture (PMID: 27636997). | 27636997 |
PIK3CA H1047R | endometrial cancer | predicted - sensitive | Alpelisib | Case Reports/Case Series | Actionable | In a clinical case study, Piqray (alpelisib) resulted in a partial response after 4 months in a patient with endometrial endometrioid cancer harboring PIK3CA H1047R, with treatment ongoing at 7 months (PMID: 36713525). | 36713525 |
PIK3CA H1047R | endometrial cancer | predicted - sensitive | Alpelisib | Case Reports/Case Series | Actionable | In a clinical study, Piqray (alpelisib) treatment was well tolerated and demonstrated activity in patients with advanced gynecologic cancer harboring activating mutations in PIK3CA and resulted in an overall response rate (ORR) of 28% (10/36), with an ORR of 35% (6/17, all partial responses) in endometrial cancer patients, including disease control in 7 of 9 patients harboring PIK3CA H1047R (PMID: 38518529; NCT04085653). | 38518529 |
PIK3CA H1047R | estrogen-receptor positive breast cancer | predicted - sensitive | Alpelisib + Everolimus | Preclinical - Patient cell culture | Actionable | In a preclinical study, combination treatment with Piqray (albelisib) and Afinitor (everolimus) synergistically inhibited cell viability of patient-derived ESR1 (ER)-positive breast cancer cells harboring PIK3CA H1047R and ESR1 (ER alpha) Y537S in culture (PMID: 36900375). | 36900375 |
PIK3CA H1047R | estrogen-receptor positive breast cancer | predicted - sensitive | 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 H1047R and ESR1 (ER alpha) Y537S in culture (PMID: 36900375). | 36900375 |
PIK3CA H1047R | ovarian cancer | predicted - sensitive | Temsirolimus | Case Reports/Case Series | Actionable | In a Phase II trial (TAPUR), Torisel (temsirolimus) treatment resulted in a partial response ongoing at 86 weeks in a patient with ovarian cancer harboring PIK3CA H1047R (J Clin Oncol 41, 2023 (suppl 16; abstr 3117); NCT02693535). | detail... |
PIK3CA H1047R | bone ameloblastoma | predicted - sensitive | 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 24.6 months and an overall survival of 25.8 months in a patient with ameloblastoma of the mandible harboring PIK3CA H1047R (PMID: 35133871; NCT02465060). | 35133871 |
PIK3CA H1047R | myxoid liposarcoma | predicted - sensitive | 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 23.7 months and an overall survival of 25.8 months in a patient with myxoid liposarcoma harboring PIK3CA H1047R (PMID: 35133871; NCT02465060). | 35133871 |
PIK3CA H1047R | head and neck squamous cell carcinoma | sensitive | Alpelisib + Tipifarnib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Piqray (alpelisib) and Zarnestra (tipifarnib) inhibited Mtor and Rsk phosphorylation, induced cell cycle arrest and apoptosis, and synergistically inhibited viability of head and neck cancer squamous cell carcinoma cell lines harboring PIK3CA H1047R in culture and inhibited Mtor signaling, induced cell cycle arrest and apoptosis, inhibited proliferation, and induced tumor regression in a cell line xenograft model (PMID: 37339176). | 37339176 |
PIK3CA H1047R | colorectal cancer | resistant | Alpelisib | Preclinical - Cell culture | Actionable | In a preclinical study, a colorectal cancer cell line harboring PIK3CA H1047R was resistant to Piqray (alpelisib) in culture (PMID: 37493631). | 37493631 |
PIK3CA H1047R | head and neck squamous cell carcinoma | sensitive | STX-478 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, STX-478 inhibited viability in head and neck squamous cell cancer cell lines harboring PIK3CA H1047R in culture, and inhibited tumor growth and induced tumor regression in a cell line xenograft model (PMID: 37623743). | 37623743 |
PIK3CA H1047R | Her2-receptor positive breast cancer | sensitive | STX-478 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, STX-478 inhibited viability in a hormone receptor-negative, ERBB2 (HER2)-positive breast cancer cell line harboring PIK3CA H1047R in culture, and inhibited tumor growth in a cell line xenograft model (PMID: 37623743). | 37623743 |
PIK3CA H1047R | Her2-receptor negative breast cancer | sensitive | STX-478 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, STX-478 inhibited viability in an ESR1-positive, ERBB2 (HER2)-negative breast cancer cell line harboring PIK3CA H1047R in culture and inhibited tumor growth and induced tumor regression with high-dose STX-478 in a cell line xenograft model and inhibited tumor growth in a patient-derived xenograft (PDX) model (PMID: 37623743). | 37623743 |
PIK3CA H1047R | Her2-receptor negative breast cancer | predicted - sensitive | 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 H1047R | breast cancer | sensitive | RLY-2608 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, RLY-2608 inhibited viability of hormone receptor-positive breast cancer cells harboring PIK3CA H1047R in culture, and inhibited tumor growth in a cell line xenograft model (PMID: 37916956). | 37916956 |
PIK3CA H1047R | Advanced Solid Tumor | predicted - sensitive | OKI-219 | Preclinical - Pdx | Actionable | In a preclinical study, OKI-219 decreased Akt phosphorylation and proliferation in tumor cell lines harboring PIK3CA H1047R in culture and inhibited tumor growth in cell line xenograft models and patient-derived xenograft (PDX) models (Mol Cancer Ther (2023) 22 (12_Supplement): B163). | detail... |
PIK3CA H1047R | Her2-receptor positive breast cancer | sensitive | ZM-PI05 | Preclinical - Cell culture | Actionable | In a preclinical study, ZM-PI05 induced cell cycle arrest and decreased viability of ERBB2 (HER2)-positive breast cancer cell lines harboring PIK3CA H1047R in culture (PMID: 38986734). | 38986734 |