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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 |
| Transcript | NM_006218 |
| 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 |
|---|---|---|---|---|---|
| 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 |
| NM_006218 | 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 |
|---|---|---|---|---|---|---|---|
| ERBB2 over exp PIK3CA H1047R | Her2-receptor positive breast cancer | sensitive | Bevacizumab + Buparlisib | Preclinical | Actionable | In a preclinical study, treatment with Buparlisib (BKM120) resulted in decreased tumor growth, but not tumor regression, in mouse models of ERBB2 (HER2)-over expressing breast cancer expressing PIK3CA H1047R (PMID: 23940356). | 23940356 |
| ERBB2 over exp PIK3CA H1047R | Her2-receptor positive breast cancer | resistant | Pertuzumab + Trastuzumab | Preclinical | Actionable | In a preclinical study, a mouse breast cancer model with ERBB2 (HER2) over-expression that also expressed the PIK3CA H1047R mutation showed resistance to the combination of Heceptin (trastuzumab) and Perjeta (pertuzumab) (PMID: 23940356). | 23940356 |
| ERBB2 over exp PIK3CA H1047R | Her2-receptor positive breast cancer | sensitive | Buparlisib + Trastuzumab | Preclinical | Actionable | In a preclinical study, the combination of Herceptin (trastuzumab) and Buparlisib (BKM120) inhibited tumor growth in mouse ERBB2 (HER2)-over expressing breast cancer models expressing PIK3CA H1047R, with moderate efficacy over Buparlisib (BKM120) alone (PMID: 23940356). | 23940356 |
| ERBB2 over exp PIK3CA H1047R | Her2-receptor positive breast cancer | resistant | Lapatinib + Trastuzumab | Preclinical | Actionable | In a preclinical study, a mouse breast cancer model with mammary ERBB2 (HER2) over-expression that also expressed the PIK3CA H1047R mutation showed resistance to the combination of Herceptin (trastuzumab) and Tykerb (lapatinib) (PMID: 23940356). | 23940356 |
| ERBB2 over exp PIK3CA H1047R | Her2-receptor positive breast cancer | no benefit | Buparlisib + Lapatinib + Trastuzumab | Preclinical | Actionable | In a preclinical study, the combination of Buparlisib (BKM120), Herceptin (trastuzumab), and Tykerb (lapatinib) inhibited tumor growth in mouse models of ERBB2 (HER2)-over expressing breast cancer expressing PIK3CA H1047R, but efficacy was not significantly improved over Buparlisib (BKM120) alone (PMID: 23940356). | 23940356 |
| ERBB2 over exp PIK3CA H1047R | Her2-receptor positive breast cancer | resistant | Trastuzumab | Preclinical | Actionable | In a preclinical study, mouse breast cancer models over expressing ERBB2 (HER2) and expressing PIK3CA H1047R were resistant to Herceptin (trastuzumab) (PMID: 23940356). | 23940356 |
| ERBB2 over exp PIK3CA H1047R | stomach cancer | predicted - resistant | Trastuzumab | Clinical Study - Cohort | Actionable | In a clinical study (AMNESIA-1), assessment of pre-treatment tumor samples from ERBB2 (HER2)-positive gastric or gastroesophageal cancer patients (defined as HER2 IHC 3+ or HER2 IHC 2+/ISH+) identified PIK3CA mutations in 15% (3/20) of patients demonstrating primary resistance to Herceptin (trastuzumab), including 1 patient harboring PIK3CA H1047R (PMID: 29208673). | 29208673 |
| ERBB2 over exp PIK3CA H1047R | Her2-receptor positive breast cancer | sensitive | Buparlisib + Pertuzumab + Trastuzumab | Preclinical | Actionable | In a preclinical study, the combination of Buparlisib (BKM120), Herceptin (trastuzumab), and Perjeta (pertuzumab) inhibited tumor growth in mouse models of ERBB2 (HER2)-over expressing breast cancer expressing PIK3CA H1047R, with improved efficacy over Buparlisib (BKM120) alone (PMID: 23940356). | 23940356 |
| 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 | 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 over expressing wild-type Pik3ca in culture (PMID: 26013318). | 26013318 |
| PIK3CA H1047R | urinary bladder cancer | sensitive | BEZ235 | 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 | 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 | stomach cancer | sensitive | Capivasertib | Preclinical - Pdx | Actionable | In a preclinical study, AZD5363 inhibited growth in a patient-derived xenograft model of gastric cancer harboring a PIK3CA H1047R mutation (PMID: 24088382). | 24088382 |
| 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 | 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 | 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 | 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 | 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 | 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 | BEZ235 | 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 | 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 | 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 | 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 | 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 | 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 | 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 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 | lung adenocarcinoma | sensitive | BEZ235 | Preclinical | Actionable | In a preclinical study, BEZ235 promoted tumor regression in a mouse lung adenocarcinoma model expressing PIK3CA H1047R (PMID: 19029981). | 19029981 |
| PIK3CA H1047R | breast cancer | sensitive | CH5132799 | Preclinical | Actionable | In a preclinical study, CH5132799 inhibited proliferation of breast cancer cells harboring PIK3CA H1047R in culture (PMID: 21558396). | 21558396 |
| 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 | 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 | 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 | 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 | 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 | ovarian cancer | sensitive | CH5132799 | Phase I | Actionable | In a Phase I trial, 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 | 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 | 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 | 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 | 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 | lung cancer | sensitive | BEZ235 | 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 squamous cell carcinoma | sensitive | BEZ235 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 4 patients harboring PIK3CA H1047R demonstrated response (PMID: 31158500; NCT02785913). | 31158500 |
| PIK3CA H1047R | thyroid gland 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 | 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 | 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 | 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 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 | 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 | 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 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 | 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 | 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 | 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 | thyroid gland 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 | breast cancer | sensitive | MK2206 | Preclinical | Actionable | In a preclinical study, MK2206 inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA H1047R in culture (PMID: 26627007). | 26627007 |
| PIK3CA P539R PIK3CA H1047R | breast cancer | sensitive | Miransertib | Preclinical - Cell culture | Actionable | In a preclinical study, breast cancer cells harboring PIK3CA P539R and H1047R were sensitive to Miransertib (ARQ092) in culture, demonstrating inhibition of cell growth (PMID: 26469692). | 26469692 |
| PIK3CA P539R PIK3CA H1047R | breast cancer | sensitive | ARQ 751 | Preclinical - Cell culture | Actionable | In a preclinical study, a breast cancer cell line harboring PIK3CA P539R and PH1047R was sensitive to ARQ 751 in culture, demonstrating inhibition of cell growth (PMID: 26469692). | 26469692 |
| PIK3CA P539R PIK3CA H1047R | breast cancer | sensitive | PF-04691502 | Preclinical - Cell culture | Actionable | In a preclinical study, PF-04691502 inhibited Akt phosphorylation and proliferation of breast cancer cells harboring both PIK3CA P539R and H1047R in culture (PMID: 21750219). | 21750219 |
| ERBB2 amp PIK3CA H1047R | breast cancer | sensitive | CH5132799 + Trastuzumab | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of CH5132799 and Herceptin (trastuzumab) inhibited tumor growth and overcame Herceptin (trastuzumab) insensitivity in xenograft models of a human breast cancer cell line harboring PIK3CA H1047R and ERBB2 (HER2) amplification (PMID: 21558396). | 21558396 |
| ERBB2 amp PIK3CA H1047R | breast cancer | sensitive | CYH33 | Preclinical - Cell culture | Actionable | In a preclinical study, CYH33 inhibited proliferation of breast cancer cell lines harboring PIK3CA H1047R and ERBB2 (HER2) amplification in culture (PMID: 30003928). | 30003928 |
| ERBB2 amp PIK3CA H1047R | ovarian cancer | sensitive | CH5132799 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, CH5132799 inhibited cell growth in a human ovarian cancer cell line harboring PIK3CA H1047R and ERBB2 (HER2) amplification, and inhibited tumor growth in xenograft models (PMID: 21558396). | 21558396 |
| ERBB2 amp PIK3CA H1047R | breast cancer | sensitive | Gedatolisib | Preclinical | Actionable | In a preclinical study, Gedatolisib (PKI-587) inhibited growth of human breast cancer cells harboring ERBB2 (HER2) amplification and PIK3CA H1047R in culture (PMID: 21325073, PMID: 17314276). | 17314276 21325073 |
| ERBB2 amp PIK3CA H1047R | breast cancer | sensitive | CH5132799 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, CH5132799 inhibited cell growth and Akt phosphorylation, and promoted apoptosis in a human breast cancer cell line harboring PIK3CA H1047R and ERBB2 (HER2) amplification, and inhibited tumor growth in xenograft models (PMID: 21558396). | 21558396 |
| ERBB2 over exp PIK3CA H1047R SRC over exp | urinary bladder cancer | no benefit | Ponatinib | Preclinical - Pdx | Actionable | In a preclinical study, treatment with Iclusig (ponatinib) was not effective in inhibiting tumor growth in a patient-derived xenograft (PDX) model of bladder cancer with SRC over expression, which also over expressed ERBB2 (HER2) and harbored PIK3CA H1047R (PMID: 26270481). | 26270481 |
| ERBB2 over exp PIK3CA H1047R SRC over exp | urinary bladder cancer | no benefit | Lapatinib | Preclinical - Pdx | Actionable | In a preclinical study, treatment with Tykerb (lapatinib) was not effective in inhibiting tumor growth in a patient-derived xenograft (PDX) model of bladder cancer with ERBB2 (HER2) over expression, which also over expressed SRC and harbored PIK3CA H1047R (PMID: 26270481). | 26270481 |
| ERBB2 pos PIK3CA H1047R | 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 |
| ERBB2 pos PIK3CA H1047R | Her2-receptor positive breast cancer | sensitive | Ado-trastuzumab emtansine | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Kadcyla (trastuzumab emtansine) inhibited survival of Herceptin (trastuzumab)-resistant ERBB2 (HER2) positive breast cancer cells harboring PIK3CA H1047R in culture, and induced tumor regression in cell line xenograft models (PMID: 26920887). | 26920887 |
| BRAF V600E PIK3CA H1047R | thyroid gland carcinoma | resistant | Everolimus | Case Reports/Case Series | Actionable | In a clinical case study, a patient with anaplastic thyroid carcinoma co-harboring BRAF V600E and PIK3CA H1047R demonstrated resistance to treatment with Afinitor (everolimus) (PMID: 27797976). | 27797976 |
| BRAF V600E PIK3CA H1047R | thyroid gland carcinoma | predicted - sensitive | Dabrafenib + Everolimus + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with anaplastic thyroid carcinoma co-harboring BRAF V600E and PIK3CA H1047R demonstrated tumor regression when treated with the triple combination, Tafinlar (dabrafenib), Mekinist (trametinib), and Afinitor (everolimus) (PMID: 27797976). | 27797976 |
| BRAF V600E PIK3CA H1047R | thyroid gland carcinoma | resistant | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with anaplastic thyroid carcinoma co-harboring BRAF V600E and PIK3CA H1047R demonstrated resistance to the combination therapy, Mekinist (trametinib) and Tafinlar (dabrafenib) (PMID: 27797976). | 27797976 |
| AKT1 over exp PIK3CA H1047R | breast cancer | resistant | Alpelisib | Preclinical - Cell culture | Actionable | In a preclinical study, Akt1 over expression in breast cancer cells harboring PIK3CA H1047R resulted in resistance to Alpelisib (BYL719) in culture (PMID: 27604488). | 27604488 |
| NRAS mut PIK3CA H1047R | melanoma | predicted - resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, one of two NRAS-mutant melanoma cell lines expressing PIK3CA H1047R demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 30819666). | 30819666 |
| PIK3CA E726K PIK3CA H1047R | breast cancer | sensitive | GDC-0077 | Preclinical - Cell culture | Actionable | In a preclinical study, breast epithelial cells expressing PIK3CA E726K and PIK3CA H1047R in cis demonstrated increased sensitivity to growth inhibition by GDC-0077 treatment compared to cells expressing individual PIK3CA mutations in culture (PMID: 31699932). | 31699932 |
| PIK3CA E726K PIK3CA H1047R | breast cancer | sensitive | Alpelisib | Preclinical - Cell culture | Actionable | In a preclinical study, breast epithelial cells expressing PIK3CA E726 and PIK3CA H1047R in cis demonstrated increased sensitivity to growth inhibition by Piqray (Alpelisib) treatment compared to cells expressing individual PIK3CA mutations in culture, while cells expressing PIK3CA E726 and PIK3CA H1047R in trans did not (PMID: 31699932). | 31699932 |
| PIK3CA E726K PIK3CA H1047R | breast cancer | sensitive | Everolimus | Preclinical - Cell culture | Actionable | In a preclinical study, breast epithelial cells expressing PIK3CA E726K and PIK3CA H1047R in cis demonstrated increased sensitivity to growth inhibition by Afinitor (everolimus) treatment compared to cells expressing individual PIK3CA mutations in culture (PMID: 31699932). | 31699932 |
| PIK3CA E453Q PIK3CA H1047R | breast cancer | sensitive | Alpelisib | Preclinical - Cell culture | Actionable | In a preclinical study, breast epithelial cells expressing PIK3CA E543Q and PIK3CA H1047R in cis demonstrated increased sensitivity to growth inhibition by Piqray (Alpelisib) treatment compared to cells expressing individual PIK3CA mutations in culture (PMID: 31699932). | 31699932 |
| PIK3CA E453Q PIK3CA H1047R | breast cancer | sensitive | GDC-0077 | Preclinical - Cell culture | Actionable | In a preclinical study, breast epithelial cells expressing PIK3CA E453Q and PIK3CA H1047R in cis demonstrated increased sensitivity to growth inhibition by GDC-0077 treatment compared to cells expressing individual PIK3CA mutations in culture (PMID: 31699932). | 31699932 |
| PIK3CA E453Q PIK3CA H1047R | breast cancer | sensitive | Everolimus | Preclinical - Cell culture | Actionable | In a preclinical study, breast epithelial cells expressing PIK3CA E453Q and PIK3CA H1047R in cis demonstrated increased sensitivity to growth inhibition by Afinitor (everolimus) treatment compared to cells expressing individual PIK3CA mutations in culture (PMID: 31699932). | 31699932 |
| ERBB2 G776V PIK3CA H1047R | ovarian cancer | sensitive | Everolimus + Neratinib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Afinitor (everolimus) to treatment with Nerlynx (neratinib) inhibited viability of an ovarian cancer cell line harboring ERBB2 (HER2) G776V and expressing PIK3CA H1047R in culture (PMID: 31978326). | 31978326 |
| ERBB2 G776V PIK3CA H1047R | ovarian cancer | resistant | Neratinib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of PIK3CA H1047R conferred resistance to Nerlynx (neratinib) in an ovarian cancer cell line harboring ERBB2 (HER2) G776V in culture (PMID: 31978326). | 31978326 |
| ERBB2 G778_P780dup PIK3CA H1047R | breast cancer | decreased response | Neratinib | Preclinical - Pdx | Actionable | In a preclinical study, Nerlynx (neratinib) resulted in a moderate delay of tumor growth in a breast cancer patient-derived xenograft model harboring ERBB2 (HER2) G778_P780dup and PIK3CA H1074R (PMID: 31978326). | 31978326 |
| ERBB2 V777L PIK3CA H1047R | breast cancer | resistant | Neratinib | Preclinical - Cell culture | Actionable | In a preclinical study, a breast cancer cell line harboring ERBB2 (HER2) V777L and PIK3CA H1047R demonstrated resistance to Nerlynx (neratinib) in culture (PMID: 31978326). | 31978326 |
| ERBB2 V777L PIK3CA H1047R | breast cancer | sensitive | Everolimus + Neratinib | Preclinical - Cell culture | Actionable | In a preclinical study, Afinitor (everolimus) and Nerlynx (neratinib) worked synergistically to inhibit viability of a breast cancer cell line harboring ERBB2 (HER2) V777L and PIK3CA H1047R in culture (PMID: 31978326). | 31978326 |
| ERBB2 L755S PIK3CA H1047R | breast cancer | sensitive | Everolimus + Neratinib | Preclinical - Cell culture | Actionable | In a preclinical study, Afinitor (everolimus) and Nerlynx (neratinib) worked synergistically to inhibit viability of a breast cancer cell line harboring ERBB2 (HER2) L755S and PIK3CA H1047R in culture (PMID: 31978326). | 31978326 |
| ERBB2 L755S PIK3CA H1047R | breast cancer | resistant | Neratinib | Preclinical - Cell culture | Actionable | In a preclinical study, a breast cancer cell line harboring ERBB2 (HER2) L755S and PIK3CA H1047R demonstrated resistance to Nerlynx (neratinib) in culture (PMID: 31978326). | 31978326 |