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| Profile Name | PIK3CA H1047R |
| 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 H1047R | 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 H1047R in culture (PMID: 26627007). | 26627007 |
| PIK3CA H1047R | 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 H1047R | breast cancer | sensitive | PIK3CA inhibitor | 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 | 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 | progesterone-receptor positive breast cancer | predicted - sensitive | mTORC1 Inhibitor | 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 | Advanced Solid Tumor | predicted - sensitive | PIK3CA inhibitor | 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 | 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 | ovarian cancer | sensitive | PIK3CA inhibitor | 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 cancer | no benefit | mTORC1 Inhibitor | 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 | Advanced Solid Tumor | sensitive | PIK3CA inhibitor | 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 | ovarian cancer | sensitive | mTOR Inhibitor PI3K Inhibitor (Pan) | 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 | breast cancer | sensitive | Akt Inhibitor (Pan) | 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 | lung cancer | sensitive | mTOR Inhibitor PI3K Inhibitor (Pan) | 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 | 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 | PIK3CA inhibitor | 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 | thyroid gland cancer | sensitive | Akt Inhibitor (Pan) mTORC1 Inhibitor | 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 metaplastic carcinoma | predicted - sensitive | PI3K Inhibitor (Pan) | 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 | Akt1 Inhibitor Akt2 Inhibitor | 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 | thyroid gland cancer | 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 an anaplastic thyroid cancer cell line harboring PIK3CA H1047R (PMID: 21289267). | 21289267 |
| PIK3CA H1047R | breast cancer | sensitive | PI3K Inhibitor (Pan) | 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 | PI3K Inhibitor (Pan) | 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 | Advanced Solid Tumor | sensitive | mTORC1 Inhibitor | 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 | mTOR Inhibitor PI3K Inhibitor (Pan) | 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 | 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 | PI3K Inhibitor (Pan) | CH5132799 | Preclinical | Actionable | In a preclinical study, CH5132799 inhibited proliferation of breast cancer cells harboring PIK3CA H1047R in culture (PMID: 21558396). | 21558396 |
| PIK3CA H1047R | breast cancer | sensitive | PIK3CA inhibitor | 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 | malignant 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 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 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 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 | lung squamous cell carcinoma | sensitive | PI3K Inhibitor (Pan) | 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 | mTOR Inhibitor PI3K Inhibitor (Pan) | 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 | 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 | lung adenocarcinoma | sensitive | mTOR Inhibitor PI3K Inhibitor (Pan) | 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 squamous cell carcinoma | sensitive | PIK3CA inhibitor | 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 | colorectal cancer | sensitive | mTOR Inhibitor | 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 | 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 | breast cancer | sensitive | mTOR Inhibitor | 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 | Akt1 Inhibitor | 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 | 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 | Akt Inhibitor (Pan) | 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 | mTOR Inhibitor PI3K Inhibitor (Pan) | 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 | PI3K Inhibitor (Pan) | 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 | ovarian cancer | sensitive | PIK3CA inhibitor | 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 | head and neck squamous cell carcinoma | sensitive | mTORC1 Inhibitor | 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 | 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 | PI3K Inhibitor (Pan) | 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 | urinary bladder cancer | sensitive | PI3K Inhibitor (Pan) | 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 | Akt Inhibitor (Pan) | 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 H1047R | lung adenocarcinoma | no benefit | mTORC1 Inhibitor | 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 | head and neck squamous cell carcinoma | sensitive | PIK3CA inhibitor | 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 | breast cancer | sensitive | Akt Inhibitor (Pan) | 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 | mTOR Inhibitor | 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 | 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 | sensitive | mTOR Inhibitor PI3K Inhibitor (Pan) | 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 | 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 | stomach cancer | sensitive | Akt Inhibitor (Pan) | 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 | estrogen-receptor positive breast cancer | predicted - sensitive | mTORC1 Inhibitor | 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 |
| Clinical Trial | Phase | Therapies | Title | Recruitment Status |
|---|---|---|---|---|
| NCT03941782 | Phase 0 | Alpelisib | Compassionate Use of BYL 719 Alpelisib | Available |