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| Gene Symbol | PTEN | ||||||||||
| Synonyms | 10q23del | BZS | CWS1 | DEC | GLM2 | MHAM | MMAC1 | PTEN1 | PTENbeta | TEP1 | ||||||||||
| Gene Description | PTEN, phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN, is a tumor suppressor (PMID: 30562755) with roles in the cell cycle, growth, DNA repair, cell survival and regulation of the Akt-mTOR pathway (PMID: 24656806, PMID: 30145641). PTEN germline mutations are common in Cowden syndrome (PMID: 30562755) and PTEN somatic alterations resulting in loss of function have been found in many types of cancer including, but not limited to endometrial (PMID: 30142194), melanoma (PMID: 30148988), and prostate (PMID: 18767981, PMID: 30153654). | ||||||||||
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| PTEN L194fs | thyroid cancer | predicted - sensitive | Ipilimumab + Nivolumab + Temsirolimus | Case Reports/Case Series | Actionable | In a clinical case study, the addition of Torisel (temsirolimus) to the combination treatment of Yervoy (ipilimumab) and Opdivo (nivolumab) resulted in a partial response with a decrease in target lesion size in a patient with poorly differentiated thyroid cancer harboring PTEN L194fs, along with TP53 F270S, who remained on treatment for 6 months (PMID: 38356955). | 38356955 |
| PIK3CA P539R PIK3CA H1047R PTEN del | breast cancer | sensitive | MEN1611 | Preclinical - Cell culture | Actionable | In a preclinical study, MEN1611 (CH5132799) inhibited viability in a breast cancer cell line with deletion of PTEN and harboring PIK3CA H1047R and P539R in culture (PMID: 36913051). | 36913051 |
| PTEN D92H PTEN F278Lfs*12 | breast cancer | sensitive | MEN1611 | Preclinical - Cell culture | Actionable | In a preclinical study, MEN1611 (CH5132799) inhibited viability in a breast cancer cell line harboring PTEN D92H and F278Lfs*12 in culture (PMID: 36913051). | 36913051 |
| PTEN L108R | breast cancer | sensitive | MEN1611 | Preclinical - Cell culture | Actionable | In a preclinical study, MEN1611 (CH5132799) inhibited viability in a breast cancer cell line harboring PTEN L108R in culture (PMID: 36913051). | 36913051 |
| PTEN F90Lfs*90 | breast cancer | sensitive | MEN1611 | Preclinical - Cell culture | Actionable | In a preclinical study, MEN1611 (CH5132799) inhibited viability in a breast cancer cell line harboring PTEN F90Lfs*90 in culture (PMID: 36913051). | 36913051 |
| PTEN del | breast cancer | sensitive | MEN1611 | Preclinical - Cell culture | Actionable | In a preclinical study, MEN1611 (CH5132799) inhibited viability in breast cancer cell lines harboring a PTEN deletion in culture (PMID: 36913051). | 36913051 |
| PTEN R142fs PTEN L265fs | ovarian cancer | sensitive | TAS0612 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, TAS0612 inhibited proliferation in a clear cell ovarian cancer cell line harboring PTEN R142fs and L265fs, along with KRAS G13C and PIK3CA H1047Y, in culture and induced tumor regression in a cell line xenograft model (PMID: 37906695). | 37906695 |
| PTEN P89fs | breast cancer | sensitive | TAS0612 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, TAS0612 inhibited proliferation in a breast cancer cell line harboring PTEN P89fs in culture and induced tumor regression in a cell line xenograft model (PMID: 37906695). | 37906695 |
| PTEN L320* | endometrial cancer | sensitive | TAS0612 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, TAS0612 inhibited proliferation in an endometrial cancer cell line harboring PTEN L320* along with ERBB2 (HER2) R896H and FGFR2 S252W in culture and induced tumor regression in a cell line xenograft model (PMID: 37906695). | 37906695 |
| PTEN K6fs | endometrial cancer | sensitive | TAS0612 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, TAS0612 inhibited proliferation in an endometrial cancer cell line harboring PTEN K6fs along with PIK3CA mutations in culture and induced tumor regression in a cell line xenograft model (PMID: 37906695). | 37906695 |
| PTEN inact mut | Advanced Solid Tumor | predicted - sensitive | Copanlisib + Nivolumab | Phase II | Actionable | In a Phase II trial (BaCoN), treatment with the combination of Aliqopa (copanlisib) and Opdivo (nivolumab) was well tolerated in patients with advanced solid tumors harboring an inactivating mutation in PTEN, and resulted in a complete response/partial response (CR/PR) in 20% (3/15, 3 cPR) and a clinical benefit rate (CR or PR or stable disease > 4 months) of 33% (Ann Oncol 34 (2023): S487-S488; NCT04317105). | detail... |
| PTEN inact mut | Advanced Solid Tumor | no benefit | Atezolizumab + Ipatasertib | Phase II | Actionable | In a Phase II trial (CRAFT), treatment with Ipatasertib (GDC-0068) plus Tecentriq (atezolizumab) demonstrated safety but limited clinical benefit in advanced solid tumor patients harboring PI3K-AKT pathway mutations (n=13), including PTEN deletion/inactivating mutations or activating mutations in PIK3CA or AKT1, with a partial response in a breast cancer patient with AKT1 E17K and stable disease in a prostate cancer patient with PTEN loss (Ann Oncol (2023) 34 (suppl_2): S256-S257;NCT04551521). | detail... |
| PTEN del | Advanced Solid Tumor | no benefit | Atezolizumab + Ipatasertib | Phase II | Actionable | In a Phase II trial (CRAFT), treatment with Ipatasertib (GDC-0068) plus Tecentriq (atezolizumab) demonstrated safety but limited clinical benefit in advanced solid tumor patients harboring PI3K-AKT pathway mutations (n=13), including PTEN deletion/inactivating mutations or activating mutations in PIK3CA or AKT1, with a partial response in a breast cancer patient with AKT1 E17K and stable disease in a prostate cancer patient with PTEN loss (Ann Oncol (2023) 34 (suppl_2): S256-S257;NCT04551521). | detail... |
| PTEN E43fs | choroid plexus carcinoma | predicted - sensitive | Everolimus | Case Reports/Case Series | Actionable | In a clinical case study, adjuvant Afinitor (everolimus) treatment after surgery and radiotherapy resulted in stable disease in a patient with choroid plexus carcinoma harboring PTEN E43fs, who completed 12 months of therapy and remained in remission at 60 months after initial diagnosis (PMID: 37535883). | 37535883 |
| PTEN inact mut | breast cancer | predicted - sensitive | AZD5991 + Capivasertib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of AZD5991 and Truqap (capivasertib) synergistically inhibited proliferation and induced apoptosis in a triple-negative breast cancer cell line and hormone-receptor positive breast cancer cell line each harboring a PTEN inactivating mutation in culture and inhibited tumor growth in cell line xenograft models (PMID: 36241868). | 36241868 |
| PTEN inact mut | breast cancer | predicted - sensitive | AZD5991 + AZD8186 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of AZD5991 and AZD8186 synergistically inhibited proliferation and induced apoptosis in a triple-negative breast cancer cell line and hormone receptor-positive breast cancer cell line each harboring a PTEN inactivating mutation in culture and inhibited tumor growth in cell line xenograft models (PMID: 36241868). | 36241868 |
| FGFR3 S249C FGFR3 amp PTEN C136fs | transitional cell carcinoma | predicted - resistant | Erdafitinib | Case Reports/Case Series | Actionable | In a clinical case study, PTEN C136fs and FGFR3 amplification (6 copies) were identified in the tissue biopsy of a patient with bladder urothelial cancer harboring FGFR3 S249C who progressed on Balversa (erdafitinib) after 1.4 months of treatment (PMID: 37377403). | 37377403 |
| PTEN loss | lung squamous cell carcinoma | predicted - resistant | unspecified PD-1 antibody | Preclinical | Actionable | In a preclinical study, a syngeneic mouse model of squamous cell lung cancer with PTEN loss demonstrated resistance to treatment with a PD-1 antibody (PMID: 37311042). | 37311042 |
| PTEN inact mut | Advanced Solid Tumor | predicted - sensitive | Temsirolimus | Phase II | Actionable | In a Phase II trial (TAPUR), Torisel (temsirolimus) treatment resulted in a disease control rate of 26% (7/27, 2 partial responses and 5 with stable disease >=16 weeks) and an objective response rate of 7% (2/27) in patients with advanced solid tumors harboring inactivating PTEN mutations, with a median progression-free survival of 10 weeks and a median overall survival of 32 weeks (Cancer Res (2023) 83 (8_Supplement): CT231; NCT02693535). | detail... |
| BRAF V600E PTEN N329fs | lung adenocarcinoma | predicted - resistant | Dabrafenib | Case Reports/Case Series | Actionable | In a clinical case study, PTEN N329fs was identified on the post-progression biopsy in a patient with metastatic lung adenocarcinoma harboring BRAF V600E, who previously responded to Tafinlar (dabrafenib) (PMID: 32388065). | 32388065 |
| PIK3CA amp PTEN H123P | triple-receptor negative breast cancer | predicted - sensitive | Afatinib + Alpelisib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, combination treatment with Piqray (albelisib) and Gilotrif (afatinib) synergistically inhibited cell viability of patient-derived triple-negative breast cancer cells harboring PIK3CA amplification and PTEN H123P in culture, and led to inhibition of tumor growth in a patient-derived xenograft (PDX) model (PMID: 36900375). | 36900375 |
| PIK3CA amp PTEN H123P | triple-receptor negative breast cancer | predicted - sensitive | Alpelisib + Everolimus | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, combination treatment with Piqray (albelisib) and Afinitor (everolimus) synergistically inhibited cell viability of patient-derived triple-negative breast cancer cells harboring PIK3CA amplification and PTEN H123P in culture, and led to inhibition of tumor growth in a patient-derived xenograft (PDX) model (PMID: 36900375). | 36900375 |
| PTEN dec exp | triple-receptor negative breast cancer | predicted - sensitive | Alpelisib + Everolimus | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, combination treatment with Piqray (albelisib) and Afinitor (everolimus) synergistically inhibited cell viability of PTEN-deficient triple-negative breast cancer patient-derived cells in culture, and led to inhibition of tumor growth in patient-derived xenograft (PDX) models (PMID: 36900375). | 36900375 |
| BRAF V600E PTEN loss | melanoma | predicted - sensitive | Dabrafenib + Enzalutamide + Trametinib | Preclinical | Actionable | In a preclinical study, addition of Xtandi (enzalutamide) to Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy improved tumor control and led to a greater reduction in tumor volume in an allograft mouse model of melanoma harboring BRAF V600E and PTEN loss (PMID: 35705814). | 35705814 |
| NRAS Q61H PTEN over exp | rhabdomyosarcoma | sensitive | Ganitumab + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Ganitumab (AMG-479) sensitized a rhabdomyosarcoma cell line harboring NRAS Q61H and overexpressing PTEN to treatment with Mekinist (trametinib), resulting in reduced cell growth in culture (PMID: 36322002). | 36322002 |
| HRAS Q61K PTEN dec exp | rhabdomyosarcoma | sensitive | Ganitumab + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Ganitumab (AMG-479) sensitized a rhabdomyosarcoma cell line harboring HRAS Q61K with low PTEN expression to treatment with Mekinist (trametinib), resulting in reduced cell growth in culture (PMID: 36322002). | 36322002 |
| HRAS Q61K PTEN dec exp | rhabdomyosarcoma | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, decreasing Pten expression through shRNA knockdown in a rhabdomyosarcoma cell line harboring HRAS Q61K conferred resistance to Mekinist (trametinib) treatment in culture (PMID: 36322002). | 36322002 |
| PIK3CA N1068Kfs*5 PTEN Y174H PTEN K263* | colorectal cancer | predicted - sensitive | Taselisib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Taselisib (GDC-0032) inhibited cell proliferation in a patient-derived colorectal cancer organoid harboring PIK3CA N1068Kfs*5, PTEN Y174H, and PTEN K263* in culture (PMID: 32376656). | 32376656 |
| PIK3CA N1068Kfs*5 PTEN Y174H PTEN K263* | colorectal cancer | predicted - sensitive | Alpelisib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Piqray (alpelisib) inhibited cell proliferation in a patient-derived colorectal cancer organoid harboring PIK3CA N1068Kfs*5, PTEN Y174H, and PTEN K263* in culture (PMID: 32376656). | 32376656 |
| PTEN Y174H PTEN K263* | colorectal cancer | predicted - sensitive | Rucaparib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Rubraca (rucaparib) inhibited cell proliferation in a patient-derived colorectal cancer organoids harboring PTEN Y174H and K263*, along with PIK3CA N1068fs, in culture (PMID: 32376656). | 32376656 |
| PTEN Y174H PTEN K263* | colorectal cancer | predicted - sensitive | Olaparib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Lynparza (olaparib) inhibited cell proliferation in a patient-derived colorectal cancer organoid harboring PTEN Y174H and K263*, along with PIK3CA N1068fs, in culture (PMID: 32376656). | 32376656 |
| PIK3CA E542K PTEN loss | 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 PTEN loss (PMID: 30093452). | 30093452 |
| PTEN inact mut | breast cancer | predicted - sensitive | TAS-117 | Case Reports/Case Series | Actionable | In a Phase II trial, TAS-117 treatment demonstrated tolerability in patients with advanced solid tumors harboring germline inactivating PTEN mutations, and resulted in an unconfirmed partial response in one patient with breast cancer and target tumor lesion shrinkage of approximately 15% and stable disease lasting more than 8 months in another breast cancer patient (Ann Oncol (2022) 33 (suppl_7): S754-S755; NCT04770246). | detail... |
| PTEN Y336* | breast cancer | sensitive | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, breast cancer cells expressing PTEN Y336* demonstrated increased sensitivity to Talzenna (talazoparib) compared to cells expressing wild-type Pten in culture (PMID: 25946202}. | 25946202 |
| HRAS G13R PTEN inact mut | Advanced Solid Tumor | predicted - sensitive | Tipifarnib | Preclinical - Cell culture | Actionable | In a preclinical study, cultured cells expressing HRAS G13R and PTEN inactivating mutations in the context of an HRAS, NRAS, and KRAS knockout were resistant to treatment with Zarnestra (tipifarnib) (Cancer Res 2022;82(12_Suppl):Abstract nr 1181). | detail... |
| HRAS G13R PTEN inact mut | Advanced Solid Tumor | predicted - sensitive | AZD8186 + Tipifarnib | Preclinical - Cell culture | Actionable | In a preclinical study, cultured cells expressing HRAS G13R and PTEN inactivating mutations in the context of an HRAS, NRAS, and KRAS knockout were sensitive to combined treatment with Zarnestra (tipifarnib) and AZD8186 (Cancer Res 2022;82(12_Suppl):Abstract nr 1181). | detail... |
| PTEN loss | clear cell renal cell carcinoma | sensitive | Temsirolimus | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Torisel (temsirolimus) inhibited cell proliferation and induced cell cycle arrest in PTEN-deficient clear cell renal carcinoma cell lines in culture and inhibited tumor growth in a cell line xenograft model (PMID: 35165399). | 35165399 |
| PTEN loss | clear cell renal cell carcinoma | sensitive | Everolimus | Preclinical - Cell culture | Actionable | In a preclinical study, Afinitor (everolimus) inhibited cell proliferation in PTEN-deficient clear cell renal carcinoma cell lines in culture (PMID: 35165399). | 35165399 |
| PTEN inact mut | head and neck cancer | predicted - sensitive | RMC-5552 | Case Reports/Case Series | Actionable | In a Phase I/Ib trial, RMC-5552 treatment resulted in an objective response rate of 20% (1/5) and 3 stable disease in patients with advanced solid tumors, with 1 partial response observed in a patient with head and neck cancer harboring a pathogenic PTEN mutation (J of Clin Oncol40, no. 16_suppl (June 01, 2022) 3098; NCT04774952). | detail... |
| PTEN loss | stomach cancer | no benefit | GSK2636771 + Paclitaxel | Phase II | Actionable | In a Phase II trial (K-Umbrella), GSK2636771 and Taxol (paclitaxel) combination therapy did not significantly improve median progression-free survival (2.9 vs 4.1 months) or median overall survival (7.4 vs 8.7 months) in patients with advanced ERBB2 (HER2)-negative gastric cancer harboring PTEN loss compared to standard of care in the control group (Journal of Clinical Oncology 40, no. 16_suppl (June 01, 2022) 4001; NCT02951091). | detail... |
| PTEN mutant | gastrointestinal system cancer | decreased response | Nivolumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, patients with MSI high, dMMR gastrointestinal tumors including gastric (n=18), colorectal (n=17), cholangiocarcinoma (n=5), small intestine (n=2), pancreatic (n=2), and duodenal cancer (n=1) harboring PTEN mutations demonstrated a decreased objective response rate (21.4 vs 54.8%), overall survival (15.2 vs 25.7 mo), and progression-free survival (4.3 vs 15.6 mo) compared to PTEN-wild-type patients when treated with Keytruda (pembrolizumab) or Opdivo (nivolumab) (PMID: 33926917). | 33926917 |
| PTEN mutant | gastrointestinal system cancer | decreased response | Pembrolizumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, patients with MSI high, dMMR gastrointestinal tumors including gastric (n=18), colorectal (n=17), cholangiocarcinoma (n=5), small intestine (n=2), pancreatic (n=2), and duodenal cancer (n=1) harboring PTEN mutations demonstrated a decreased objective response rate (21.4 vs 54.8%), overall survival (15.2 vs 25.7 mo), and progression-free survival (4.3 vs 15.6 mo) compared to PTEN-wild-type patients when treated with Keytruda (pembrolizumab) or Opdivo (nivolumab) (PMID: 33926917). | 33926917 |
| PTEN N323fs | castration-resistant prostate carcinoma | predicted - sensitive | Everolimus | Case Reports/Case Series | Actionable | In a clinical case study, Afinitor (everolimus) treatment resulted in stable disease for eight months in a patient with castration-resistant prostate cancer harboring PTEN N323fs*21 who had previously progressed on several lines of therapy (PMID: 32399016). | 32399016 |
| PTEN inact mut | glioblastoma | predicted - sensitive | Atezolizumab + Ipatasertib | Phase I | Actionable | In a Phase I trial (Ice-CAP), combination treatment with Ipatasertib (GDC-0068) and Tecentriq (atezolizumab) demonstrated safety and tolerability in glioblastoma patients harboring PTEN loss or PTEN mutations, and led to a clinical benefit rate of 29% (2/7), with 1 pathological complete response, and stable disease in 1 patient of 7 patients (Cancer Res 2021;81(13_Suppl):Abstract nr CT120; NCT03673787). | detail... |
| PTEN loss | glioblastoma | predicted - sensitive | Atezolizumab + Ipatasertib | Phase I | Actionable | In a Phase I trial (Ice-CAP), the combination of Ipatasertib (GDC-0068) and Tecentriq (atezolizumab) resulted in a clinical benefit rate (CBR) of 32% (6/19) in patients with glioblastoma, and CBR was 28.6% (4/14) in patients with PTEN loss as determined by IHC (H<30) (Cancer Res (2023) 83 (8_Supplement): CT093; NCT03673787). | detail... |
| CHEK2 inact mut FANCA inact mut PTEN inact mut | Her2-receptor negative breast cancer | predicted - sensitive | Talazoparib | Case Reports/Case Series | Actionable | In a Phase II trial, Talzenna (talazoparib) treatment was well tolerated, and among 12 evaluable ERBB2 (HER2)-negative breast cancer patients with a homologous repair pathway mutation resulted in response in 25% (3/12) of patients, including a patient with germline mutations in CHEK2 and FANCA, and a somatic PTEN mutation (J Clin Oncol 37, no. 15_suppl (May 20, 2019) 3006). | detail... |
| PTEN inact mut | castration-resistant prostate carcinoma | predicted - sensitive | CC-115 + Enzalutamide | Phase I | Actionable | In a Phase Ib trial, Xtandi (enzalutamide) plus CC-115 was safe and led to a PSA reduction >= 50% (PSA50) in 80% (32/40) and >=90% (PSA90) in 58% (23/40) of patients with metastatic castration-resistant prostate cancer at 12 weeks, and patients harboring PTEN mutation or deletion (n=11) achieved PSA50 of 91%, PSA90 of 55%, and median radiographic progression-free survival was not reached, compared to 75%, 55%, and 19.6 mo, respectively, in PTEN wild-type patients (n=20) (PMID: 37980367; NCT02833883). | 37980367 |
| PTEN loss | castration-resistant prostate carcinoma | no benefit | Enzalutamide + GSK2636771 | Phase I | Actionable | In a Phase I trial, combination GSK2636771 and Xtandi (enzalutamide) was safe and tolerable in patients with castration-resistant prostate cancer with PTEN deficiency, but resulted in limited antitumor activity in patients who had previously progressed on Xtandi (enzalutamide), with a 12-week non-progressive disease (non-PD) rate of 50% and a best response of 1 partial response, stable disease in 33% (12/36), non-complete response/non-PD in 22% (8/36), and PD in 28% (10/36) (PMID: 34281912; NCT02215096). | 34281912 |
| PTEN L108R | breast cancer | predicted - sensitive | GSK690693 | Preclinical - Cell culture | Actionable | In a preclinical study, GSK690693 treatment did not increase cell death but inhibited proliferation of a breast cancer cell line harboring PTEN L108R in culture (PMID: 32439931). | 32439931 |
| PTEN L108R | breast cancer | sensitive | ARQ 751 | Preclinical - Cell culture | Actionable | In a preclinical study, ARQ 751 treatment increased cell death and inhibited proliferation of a breast cancer cell line harboring PTEN L108R in culture (PMID: 32439931). | 32439931 |
| PTEN loss | prostate cancer | predicted - sensitive | Carboplatin + Paclitaxel + Sapanisertib | Case Reports/Case Series | Actionable | In a Phase I trial, combination treatment with Paraplatin (carboplatin), Taxol (paclitaxel), and Sapanisertib (MLN0128) led to a partial response in a castrate resistant prostate cancer harboring PTEN loss (Cancer Res 2021;81(13_Suppl):Abstract nr CT109; NCT03430882). | detail... |
| PTEN del | prostate cancer | sensitive | RER | Preclinical | Actionable | In a preclinical study, RER treatment inhibited Tgf-beta and Akt pathways signaling, led to inhibition of tumor cell proliferation and tumorigenesis in a PTEN knock-out mouse model of prostate cancer (PMID: 27863384). | 27863384 |
| PTEN inact mut | endometrial cancer | no benefit | LY3023414 | Phase II | Actionable | In a Phase II trial, patients with advanced endometrial cancer harboring a PI3K pathway mutation, including PTEN inactivating mutations, demonstrated only a modest clinical benefit with an overall response rate of 16% (4/25), a clinical benefit rate of 28% (7/25) at 12 weeks, a progression-free survival of 2.5 months, and overall survival of 9.2 months when treated with LY3023414 (PMID: 31880826; NCT01775072). | 31880826 |
| PTEN inact mut | triple-receptor negative breast cancer | no benefit | Ipatasertib + Paclitaxel | Phase II | Actionable | In a Phase II trial (LOTUS), Ipatasertib (GDC-0068) in combination with Abraxane (paclitaxel) resulted a median progression free survival of 6.2 vs 4.9 months with placebo in triple-receptor negative breast cancer patients harboring activating mutations in PIK3CA or AKT1, or inactivating mutations in PTEN (PMID: 28800861; NCT02162719). | 28800861 |
| PTEN inact mut | triple-receptor negative breast cancer | no benefit | Ipatasertib + Paclitaxel | Phase III | Actionable | In a Phase III trial (IPATunity 130), the addition of Ipatasertib (GDC-0068) to treatment with Abraxane (paclitaxel) did not result in improved progression-free survival in patients with triple-negative breast cancer harboring PIK3CA and/or AKT activating mutations or PTEN alterations, with a median PFS of 7.4 months with Ipatasertib (GDC-0068) plus Abraxane (paclitaxel) vs. 6.1 months with placebo plus Abraxane (paclitaxel) (SABCS 2020, Abstract GS3-04; NCT03337724). | detail... |
| PTEN del | endometrial carcinoma | sensitive | Buparlisib + Olaparib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Buparlisib (BKM120) and Lynparza (olaparib) resulted in enhanced DNA damage and growth inhibition in an endometrial carcinoma cell line with PTEN knocked out via CRISPR/Cas9 system in culture (PMID: 28945226). | 28945226 |
| PTEN del | endometrial carcinoma | sensitive | Buparlisib | Preclinical - Cell culture | Actionable | In a preclinical study, Buparlisib (BKM120) inhibited Akt signaling, induced DNA damage, and inhibited the growth of an endometrial carcinoma cell line with PTEN knocked out via CRISPR/Cas9 system in culture (PMID: 28945226). | 28945226 |
| PTEN del | endometrial carcinoma | no benefit | Olaparib | Preclinical - Cell culture | Actionable | In a preclinical study, Lynparza (olaparib) treatment did not significantly increase DNA damage or inhibit growth of an endometrial carcinoma cell line with PTEN knocked out via CRISPR/Cas9 system in culture (PMID: 28945226). | 28945226 |
| PTEN negative | endometrial carcinoma | sensitive | Buparlisib + Olaparib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Buparlisib (BKM120) and Lynparza (olaparib) resulted in enhanced DNA damage and growth inhibition in PTEN-deficient endometrial carcinoma cell lines in culture (PMID: 28945226). | 28945226 |
| PTEN negative | endometrial carcinoma | sensitive | Buparlisib | Preclinical - Cell culture | Actionable | In a preclinical study, Buparlisib (BKM120) inhibited Akt signaling, induced DNA damage, and inhibited the growth of PTEN-deficient endometrial carcinoma cell lines in culture (PMID: 28945226). | 28945226 |
| PTEN negative | endometrial carcinoma | no benefit | Olaparib | Preclinical - Cell culture | Actionable | In a preclinical study, Lynparza (olaparib) treatment did not significantly increase DNA damage or inhibit growth of PTEN-deficient endometrial carcinoma cell lines in culture (PMID: 28945226). | 28945226 |
| PTEN mutant | Advanced Solid Tumor | no benefit | Talazoparib | Phase II | Actionable | In a Phase II trial, Talzenna (talazoparib) treatment did not result in significant clinical benefit in patients with advanced solid tumors harboring PTEN mutation or loss (by IHC), with one patient harboring a PTEN mutation achieved a prolonged stable disease as best response in a cohort of 13 patients (Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A096; NCT02286687). | detail... |
| PIK3CA H1047R PTEN loss | breast cancer | sensitive | Taselisib | Preclinical - Cell culture | Actionable | In a preclinical study, a breast cancer cell line harboring a PIK3CA H1047R and PTEN loss was sensitive to treatment with Taselisib (GDC-0032) in culture, demonstrating decreased cell viability (PMID: 31534012). | 31534012 |
| PIK3CA E542K PTEN loss | breast cancer | sensitive | Taselisib | Preclinical - Cell culture | Actionable | In a preclinical study, a breast cancer cell line harboring PIK3CA E542K was sensitive to treatment with Taselisib (GDC-0032) in culture, demonstrating decreased cell viability (PMID: 31534012). | 31534012 |
| PTEN loss | glioblastoma | sensitive | AZD5991 + Temozolomide | Preclinical - Cell culture | Actionable | In a preclinical study, AZD5991 in combination with Temodar (temozolomide) synergistically inhibited proliferation of PTEN-deficient glioblastoma cells in culture (PMID: 32737157). | 32737157 |
| PTEN loss | glioblastoma | sensitive | Temozolomide + UMI-77 | Preclinical - Cell culture | Actionable | In a preclinical study, UMI-77 in combination with Temodar (temozolomide) enhanced cytotoxicity and apoptosis, and synergistically inhibited proliferation of PTEN-deficient glioblastoma cells in culture (PMID: 32737157). | 32737157 |
| PTEN loss | glioblastoma | sensitive | AZD5991 | Preclinical - Cell culture | Actionable | In a preclinical study, AZD5991 treatment inhibited proliferation of PTEN-deficient glioblastoma cells in culture (PMID: 32737157). | 32737157 |
| PTEN loss | glioblastoma | sensitive | S63845 | Preclinical - Cell culture | Actionable | In a preclinical study, S63845 treatment reduced Akt phosphorylation and inhibited proliferation of PTEN-deficient glioblastoma cells in culture (PMID: 32737157). | 32737157 |
| PTEN loss | glioblastoma | sensitive | A-1210477 | Preclinical - Cell culture | Actionable | In a preclinical study, A-1210477 treatment reduced Akt phosphorylation and inhibited proliferation of PTEN-deficient glioblastoma cells in culture (PMID: 32737157). | 32737157 |
| PTEN loss | glioblastoma | sensitive | UMI-77 | Preclinical - Cell culture | Actionable | In a preclinical study, UMI-77 treatment led to enhanced apoptosis, reduced Akt phosphorylation, and inhibited proliferation, colony formation, spheroid formation, and neurosphere formation in PTEN-deficient glioblastoma cell lines in culture (PMID: 32737157). | 32737157 |
| PTEN loss | glioblastoma | predicted - sensitive | Birinapant | Preclinical - Cell culture | Actionable | In a preclinical study, TL32711 (birinapant) treatment inhibited proliferation of PTEN-deficient glioblastoma cells in culture (PMID: 32737157). | 32737157 |
| PTEN loss | glioblastoma | predicted - sensitive | GDC-0152 | Preclinical - Cell culture | Actionable | In a preclinical study, GDC-0152 treatment inhibited proliferation of PTEN-deficient glioblastoma cells in culture (PMID: 32737157). | 32737157 |
| PTEN dec exp | stomach cancer | no benefit | Fluorouracil + Ipatasertib + Leucovorin + Oxaliplatin | Phase II | Actionable | In a Phase II trial, the combination of Ipatasertib (GDC-0068) and mFOLFOX6 did not improve median progression-free survival (7.1 vs 7.4 months; HR=1.07, p=0.86) compared to placebo plus mFOLFOX6 in patients with advanced gastric or gastroesophageal junction cancer harboring decreased PTEN expression (IHC=0 in >10% of tumor cells) (PMID: 30592991; NCT01896531). | 30592991 |
| PTEN dec exp | gastroesophageal cancer | no benefit | Fluorouracil + Ipatasertib + Leucovorin + Oxaliplatin | Phase II | Actionable | In a Phase II trial, the combination of Ipatasertib (GDC-0068) and mFOLFOX6 did not improve median progression-free survival (7.1 vs 7.4 months; HR=1.07, p=0.86) compared to placebo plus mFOLFOX6 in patients with advanced gastroesophageal junction or gastric cancer harboring decreased PTEN expression (IHC=0 in >10% of tumor cells) (PMID: 30592991; NCT01896531). | 30592991 |
| PTEN L152P PTEN neg | salivary gland carcinoma | sensitive | Pictilisib | Preclinical - Cell culture | Actionable | In a preclinical study, Pictilisib (GDC-0941) inhibited Akt phosphorylation and proliferation of salivary ductal carcinoma cells harboring PTEN L152P and loss of Pten protein expression in culture (PMID: 30289966). | 30289966 |
| PTEN L152P PTEN neg | salivary gland carcinoma | sensitive | Alpelisib + AZD8186 | Preclinical - Cell culture | Actionable | In a preclinical study, combination of Piqray (Alpelisib) and AZD8186 inhibited Akt phosphorylation and proliferation of salivary ductal carcinoma cells harboring PTEN L152P and loss of Pten protein expression in culture (PMID: 30289966). | 30289966 |
| PTEN L152P PTEN neg | salivary gland carcinoma | resistant | Alpelisib | Preclinical - Cell culture | Actionable | In a preclinical study, salivary ductal carcinoma cells harboring PTEN L152P and loss of Pten protein expression were resistant to Piqray (Alpelisib)-induced inhibition of Akt phosphorylation and proliferation in culture (PMID: 30289966). | 30289966 |
| PTEN L152P PTEN neg | salivary gland carcinoma | resistant | GSK2636771 | Preclinical - Cell culture | Actionable | In a preclinical study, salivary ductal carcinoma cells harboring PTEN L152P and loss of Pten protein expression were resistant to GSK2636771-induced inhibition of proliferation in culture (PMID: 30289966). | 30289966 |
| PTEN L152P PTEN neg | salivary gland carcinoma | resistant | AZD8186 | Preclinical - Cell culture | Actionable | In a preclinical study, salivary ductal carcinoma cells harboring PTEN L152P and loss of Pten protein expression were resistant to AZD8186-induced inhibition of Akt phosphorylation and proliferation in culture (PMID: 30289966). | 30289966 |
| PTEN R130* | Her2-receptor negative breast cancer | predicted - resistant | Alpelisib + Letrozole | Case Reports/Case Series | Actionable | In a Phase I/II trial, combination of Piqray (Alpelisib) and Femara (letrozole) resulted in no clinical benefit in a patient with hormone receptor positive, ERBB2 (HER2)-negative breast cancer harboring PTEN R130* (PMID: 32864625; NCT01870505). | 32864625 |
| PTEN LOH | transitional cell carcinoma | predicted - sensitive | Buparlisib | Case Reports/Case Series | Actionable | In a Phase II trial, Buparlisib (BKM120) treatment resulted in stable disease in a patient with metastatic urothelial carcinoma harboring PTEN loss of heterozygosity (PMID: 32767682; NCT01551030). | 32767682 |
| PTEN del | prostate cancer | not predictive | PX-866 | Phase II | Actionable | In a Phase II trial, Sonolisib (PX-866) treatment resulted in stable disease as best response in 66.7% (2/3) of patients with recurrent or metastatic castration-resistant prostate cancer harboring homozygous PTEN deletion, while in PTEN wild-type patients resulted in a partial response in 14.3% (2/14) and stable disease in 28.6% (4/14) of patients (PMID: 31056399). | 31056399 |
| PTEN loss | triple-receptor negative breast cancer | predicted - sensitive | Capivasertib + Paclitaxel | Phase II | Actionable | In a Phase II trial (PAKT), addition of Truqap (capivasertib) to Taxol (paclitaxel) as first-line therapy significantly improved median progression-free survival (9.3 vs 3.7 months, HR=0.30, p=0.01) and reduced risk (66%, HR=0.34, p=0.04) compared to Taxol (paclitaxel) alone in patients with metastatic triple-negative breast cancer harboring activating mutations in AKT1 (n=1) or PIK3CA (n=17), or inactivating mutations or gene loss in PTEN (n=13) (PMID: 31841354; NCT02423603). | 31841354 |
| PTEN loss | stomach cancer | sensitive | Ipatasertib | Preclinical - Pdx | Actionable | In a preclinical study, Ipatasertib (GDC-0068) demonstrated activity against tumor growth in patient-derived xenograft (PDX) models of ERBB2 (HER2)-negative stomach cancer harboring PTEN loss (PMID: 32205017). | 32205017 |
| PTEN loss | stomach cancer | sensitive | Fluorouracil + Ipatasertib + Leucovorin + Oxaliplatin | Preclinical - Pdx | Actionable | In a preclinical study, the combination of Ipatasertib (GDC-0068) and FOLFOX inhibited tumor growth in a patient-derived xenograft (PDX) model of ERBB2 (HER2)-negative gastric cancer harboring PTEN loss, and demonstrated increased activity over either agent alone (PMID: 32205017). | 32205017 |
| PTEN dec exp | triple-receptor negative breast cancer | sensitive | Ipatasertib | Preclinical - Pdx | Actionable | In a preclinical study, Ipatasertib (GDC-0068) reduced tumor growth in a patient-derived xenograft (PDX) model of triple-negative breast cancer with low PTEN expression (PMID: 32205017). | 32205017 |
| PTEN dec exp | triple-receptor negative breast cancer | sensitive | Docetaxel + Ipatasertib | Preclinical - Pdx | Actionable | In a preclinical study, the combination of Ipatasertib (GDC-0068) and Taxotere (docetaxel) inhibited tumor growth in a patient-derived xenograft (PDX) model of triple-negative breast cancer with low PTEN expression, and demonstrated increased activity over either agent alone (PMID: 32205017). | 32205017 |
| PTEN mutant | lung adenocarcinoma | no benefit | Capivasertib | Case Reports/Case Series | Actionable | In a Phase II trial (NLMT), Truqap (capivasertib) treatment did not result in a confirmed response (0/8) or durable clinical benefit (0/8) in patients with lung adenocarcinoma harboring mutations in PIK3CA, PTEN, or AKT, thus the cohort was closed due to futility (PMID: 32669708, NCT02664935). | 32669708 |
| PTEN loss | lung squamous cell carcinoma | no benefit | Capivasertib | Case Reports/Case Series | Actionable | In a Phase II trial (NLMT), Truqap (capivasertib) treatment did not result in a confirmed response (0/4) or durable clinical benefit (0/2) in patients with squamous cell lung cancer harboring PTEN loss, thus the cohort was closed due to futility (PMID: 32669708, NCT02664935). | 32669708 |
| BRAF V600E PIK3CA H1047R PTEN Y68fs | melanoma | predicted - resistant | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical study, a melanoma patient harboring BRAF V600E and PTEN Y68fs treated with Zelboraf (vemurafenib) was found to have acquired PIK3CA H1047R in the post-progression tumor biopsy (PMID: 24265153). | 24265153 |
| PTEN loss | breast cancer | sensitive | Fulvestrant + MK2206 + Ribociclib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Kisqali (ribociclib), Faslodex (fulvestrant), and MK2206 inhibited growth of PTEN-deficient breast cancer cells in culture (PMID: 31594766). | 31594766 |
| PTEN loss | breast cancer | sensitive | Ipatasertib + Palbociclib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Ibrance (palbociclib) and Ipatasertib (GDC-0068) inhibited growth of PTEN-deficient breast cancer cells in culture (PMID: 31594766). | 31594766 |
| PTEN loss | breast cancer | sensitive | MK2206 + Palbociclib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Ibrance (palbociclib) and MK2206 inhibited growth of PTEN-deficient breast cancer cells in culture (PMID: 31594766). | 31594766 |
| PTEN loss | breast cancer | sensitive | Ipatasertib + Ribociclib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Ipatasertib (GDC-0068) and Kisqali (ribociclib) induced cell cycle arrest and inhibited growth of PTEN-deficient breast cancer cells in culture (PMID: 31594766). | 31594766 |
| PTEN loss | breast cancer | sensitive | MK2206 + Ribociclib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination treatment of MK2206 and Kisqali (ribociclib) induced cell cycle arrest and inhibited cell proliferation of PTEN-deficient breast cancer cells in culture and led to tumor regression in cell-line xenograft models (PMID: 31594766). | 31594766 |
| PTEN loss | breast cancer | resistant | Fulvestrant + Ribociclib | Preclinical - Cell culture | Actionable | In a preclinical study, PTEN-deficient breast cancer cells demonstrated resistance to the combination of Kisqali (ribociclib) and Faslodex (fulvestrant) in culture (PMID: 31594766). | 31594766 |
| PTEN loss | breast cancer | predicted - resistant | Ribociclib | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with Kisqali (ribociclib) resulted in a decreased response in two PTEN-deficient breast cancer cell lines in culture compared to control cells and resistance in a cell-line xenograft model (PMID: 31594766). | 31594766 |
| PTEN loss | breast cancer | decreased response | Palbociclib | Preclinical - Cell culture | Actionable | In a preclinical study, two PTEN-deficient breast cancer cell lines demonstrated a decreased response to treatment with Ibrance (palbociclib) compared to control cells in culture (PMID: 31594766). | 31594766 |
| PTEN negative | glioblastoma | no benefit | Buparlisib + Capmatinib | Phase Ib/II | Actionable | In a Phase Ib/II trial, combination of Buparlisib (BKM120) and Tabrecta (capmatinib) did not reach target exposure due to potential drug-drug interaction, and demonstrated minimal activity in patients with glioblastoma harboring PTEN alterations including deletion, mutation, or negative protein expression, therefore, Phase II of the trial was not initiated (PMID: 31776899; NCT01870726). | 31776899 |
| PTEN mutant | glioblastoma | no benefit | Buparlisib + Capmatinib | Phase Ib/II | Actionable | In a Phase Ib/II trial, combination of Buparlisib (BKM120) and Tabrecta (capmatinib) did not reach target exposure due to potential drug-drug interaction, and demonstrated minimal activity in patients with glioblastoma harboring PTEN alterations including deletion, mutation, or negative protein expression, therefore, Phase II of the trial was not initiated (PMID: 31776899; NCT01870726). | 31776899 |
| PTEN del | glioblastoma | no benefit | Buparlisib + Capmatinib | Phase Ib/II | Actionable | In a Phase Ib/II trial, combination of Buparlisib (BKM120) and Tabrecta (capmatinib) did not reach target exposure due to potential drug-drug interaction, and demonstrated minimal activity in patients with glioblastoma harboring PTEN alterations including deletion, mutation, or negative protein expression, therefore, Phase II of the trial was not initiated (PMID: 31776899; NCT01870726). | 31776899 |
| BRAF V600E PTEN del | melanoma | predicted - resistant | Dabrafenib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) treatment in a metastatic melanoma patient harboring BRAF V600E and PTEN deletion resulted in disease progression after 2.8 months following an initial partial response (PMID: 31980996). | 31980996 |
| BRAF V600E PTEN Y27C | melanoma | predicted - resistant | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, Zelboraf (vemurafenib) treatment in a metastatic melanoma patient harboring BRAF V600E and PTEN Y27C resulted in disease progression after 2.3 months following an initial partial response (PMID: 31980996). | 31980996 |
| PTEN loss | osteosarcoma | sensitive | Sirolimus | Preclinical - Pdx | Actionable | In a preclinical study, a patient derived xenograft (PDX) model of osteosarcoma with biallelic PTEN loss was sensitive to treatment with Rapamune (sirolimus), demonstrating reduced tumor growth and increased apoptotic activity (PMID: 30266815). | 30266815 |
| PTEN loss | osteosarcoma | sensitive | MK2206 | Preclinical - Pdx | Actionable | In a preclinical study, a patient derived xenograft (PDX) model of osteosarcoma with biallelic loss of PTEN was sensitive to treatment with MK2206, demonstrating reduced tumor growth and increased apoptotic activity (PMID: 30266815). | 30266815 |
| PTEN negative | prostate cancer | not predictive | Niraparib | Phase I | Actionable | In a Phase I trial, negative PTEN IHC staining was not associated with response to Zejula (niraparib) treatment in patients with castration-resistant prostate cancer (PMID: 23810788; NCT00749502). | 23810788 |
| PTEN inact mut | lung non-small cell carcinoma | predicted - resistant | Osimertinib | Case Reports/Case Series | Actionable | In a retrospective analysis, inactivating PTEN mutations were identified in 3 of 100 patients with non-small cell lung cancer at treatment discontinuation of Tagrisso (osimertinib) (PMID: 31839416). | 31839416 |
| PTEN negative | renal cell carcinoma | predicted - sensitive | Everolimus | Clinical Study - Cohort | Actionable | In a clinical study, negative PTEN IHC staining were detected more frequently in patients with renal cell carcinoma who responded to treatment with Afinitor (everolimus) or Torisel (temsirolimus) (odds ratio = 0.24, p=0.029) than those who did not respond (PMID: 31335987). | 31335987 |
| PTEN negative | renal cell carcinoma | predicted - sensitive | Temsirolimus | Clinical Study - Cohort | Actionable | In a clinical study, negative PTEN IHC staining were detected more frequently in patients with renal cell carcinoma who responded to treatment with Afinitor (everolimus) or Torisel (temsirolimus) (odds ratio = 0.24, p=0.029) than those who did not respond (PMID: 31335987). | 31335987 |
| PTEN L108R | breast cancer | sensitive | Ipatasertib | Preclinical - Cell culture | Actionable | In a preclinical study, Ipatasertib (GDC-0068) inhibited proliferation of a breast cancer cell line harboring PTEN L108R in culture (PMID: 30858154). | 30858154 |
| PTEN L108R | breast cancer | sensitive | Ipatasertib | Preclinical - Cell culture | Actionable | In a preclinical study, Ipatasertib (GDC-0068) treatment increased cell death and inhibited proliferation of a breast cancer cell line harboring PTEN L108R in culture (PMID: 32439931). | 32439931 |
| PTEN L108R | breast cancer | sensitive | MK2206 | Preclinical - Cell culture | Actionable | In a preclinical study, MK-2206 inhibited proliferation of a breast cancer cell line harboring PTEN L108R in culture (PMID: 30858154). | 30858154 |
| PTEN L108R | breast cancer | sensitive | MK2206 | Preclinical - Cell culture | Actionable | In a preclinical study, MK2206 treatment increased cell death and inhibited proliferation of a breast cancer cell line harboring PTEN L108R in culture (PMID: 32439931). | 32439931 |
| PTEN L108R | breast cancer | sensitive | Capivasertib | Preclinical - Cell culture | Actionable | In a preclinical study, Truqap (capivasertib) inhibited proliferation of a breast cancer cell line harboring PTEN L108R in culture (PMID: 30858154). | 30858154 |
| PTEN L108R | breast cancer | sensitive | Miransertib | Preclinical - Cell culture | Actionable | In a preclinical study, Miransertib (ARQ092) inhibited proliferation of a breast cancer cell line harboring PTEN L108R in culture (PMID: 30858154). | 30858154 |
| PTEN L108R | breast cancer | sensitive | Miransertib | Preclinical - Cell culture | Actionable | In a preclinical study, Miransertib (ARQ092) treatment increased cell death and inhibited proliferation of a breast cancer cell line harboring PTEN L108R in culture (PMID: 32439931). | 32439931 |
| PTEN L108R | breast cancer | sensitive | Borussertib | Preclinical - Cell culture | Actionable | In a preclinical study, borussertib inhibited AKT signaling and proliferation and increased apoptosis in a breast cancer cell line harboring PTEN L108R in culture (PMID: 30858154). | 30858154 |
| BRAF V600E PTEN loss | melanoma | sensitive | unspecified PD-1 antibody + VE800 | Preclinical | Actionable | In a preclinical study, PD-1 antibody treatment supplemented with VE800 inhibited tumor growth in a transgenic mouse model of melanoma harboring PTEN loss and BRAF V600E (PMID: 30675064). | 30675064 |
| PIK3CA E542K PTEN loss | breast cancer | predicted - sensitive | CYH33 | Preclinical - Cell culture | Actionable | In a preclinical study, CYH33 inhibited proliferation of a breast cancer cell line harboring PIK3CA E542K and PTEN loss in culture (PMID: 30003928). | 30003928 |
| PIK3CA H1047R PTEN loss | breast cancer | predicted - sensitive | CYH33 | Preclinical - Cell culture | Actionable | In a preclinical study, CYH33 inhibited proliferation of a breast cancer cell line harboring PIK3CA H1047R and PTEN loss in culture (PMID: 30003928). | 30003928 |
| PTEN loss | breast cancer | no benefit | CYH33 | Preclinical - Cell culture | Actionable | In a preclinical study, PTEN loss was not associated with sensitivity to CYH33 in breast cancer cell lines in culture (PMID: 30003928). | 30003928 |
| PTEN loss | breast cancer | no benefit | MK2206 | Phase II | Actionable | In a Phase II trial, MK2206 treatment resulted in no objective response and 1 stable disease in 7 patients with advanced breast cancer harboring PTEN loss (PMID: 31277699; NCT01277757). | 31277699 |
| PTEN inact mut | triple-receptor negative breast cancer | predicted - sensitive | Capivasertib + Paclitaxel | Phase II | Actionable | In a Phase II trial (PAKT), addition of Truqap (capivasertib) to Taxol (paclitaxel) as first-line therapy significantly improved median progression-free survival (9.3 vs 3.7 months, HR=0.30, p=0.01) and reduced risk (66%, HR=0.34, p=0.04) compared to Taxol (paclitaxel) alone in patients with metastatic triple-negative breast cancer harboring activating mutations in AKT1 (n=1) or PIK3CA (n=17), or inactivating mutations or gene loss in PTEN (n=13) (PMID: 31841354; NCT02423603). | 31841354 |
| PTEN positive | head and neck squamous cell carcinoma | predicted - sensitive | Cetuximab | Clinical Study - Cohort | Actionable | In a clinical study, high PTEN expression was associated with improved progression-free survival (HR=0.35, p=0.008) in head and neck squamous cell carcinoma patients treated with Erbitux (cetuximab) with or without Nexavar (sorafenib) (PMID: 30926065). | 30926065 |
| PIK3CA wild-type PTEN pos | head and neck squamous cell carcinoma | predicted - sensitive | Cetuximab + Cisplatin | Clinical Study - Cohort | Actionable | In a clinical study, combination of Erbitux (cetuximab) with Platinol (cisplatin) tended to improve progression-free survival compared to placebo in PTEN-expressing, PIK3CA wild-type head and neck squamous cell carcinoma patients (HR=0.54, p=0.0502) by multivariable analysis, but not in PTEN null or PIK3CA mutated patients (HR=0.76, p=0.54) (PMID: 30926065). | 30926065 |
| PTEN mutant | hepatocellular carcinoma | decreased response | Sorafenib | Clinical Study - Cohort | Actionable | In a clinical case study, Nexavar (sorafenib) treatment of patients with hepatocellular carcinoma harboring Mtor pathway mutations in PIK3CA, PTEN, TSC2, or TSC1 (n=12), resulted in a lower disease control rate (8.3% vs. 40.2%), shorter progression-free survival (1.9 months vs. 5.3 months) and shorter overall survival (10.4 months vs. 17.9 months) compared to patients without mutations in this pathway (n=67) (PMID: 30373752; NCT01775072). | 30373752 |
| IDH1 wild-type PTEN mut | glioblastoma | resistant | Nivolumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, PTEN mutations were significantly enriched in patients with IDH1 wild-type glioblastoma who did not respond to anti-PD-1 therapy with either Keytruda (pembrolizumab) or Opdivo (nivolumab), compared to those who responded (odds ratio=0.85, p=0.0063), with 23 PTEN mutations identified in 32 non-responders and 3 in 13 responders (PMID: 30742119). | 30742119 |
| IDH1 wild-type PTEN mut | glioblastoma | resistant | Pembrolizumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, PTEN mutations were significantly enriched in patients with IDH1 wild-type glioblastoma who did not respond to anti-PD-1 therapy, with either Keytruda (pembrolizumab) or Opdivo (nivolumab), compared to those who responded (odds ratio=0.85, p=0.0063), with 23 PTEN mutations identified in 32 non-responders and 3 in 13 responders (PMID: 30742119). | 30742119 |
| CDKN2A loss PIK3CA E542K PTEN loss | 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 PTEN loss, with p16 (CDKN2A) loss (PMID: 30093452). | 30093452 |
| PIK3CA E542K PTEN loss | 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 PTEN loss (PMID: 30093452). | 30093452 |
| PTEN loss | lung squamous cell carcinoma | no benefit | Buparlisib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, lung squamous cell carcinoma patient-derived xenograft (PDX) models harboring PTEN loss did not respond to Buparlisib (BKM120) treatment (PMID: 30093452). | 30093452 |
| PTEN loss | renal cell carcinoma | predicted - sensitive | Everolimus | Clinical Study - Cohort | Actionable | In a retrospective analysis, loss of PTEN expression was associated with improved progression-free survival compared to PTEN positive (10.5 vs 5.3 months) in renal cell carcinoma patients treated with Afinitor (everolimus) (PMID: 30327302). | 30327302 |
| KIT Y570_L576del KIT D816E PTEN T321fs | gastrointestinal stromal tumor | sensitive | Imatinib + LY294002 | Preclinical - Pdx | Actionable | In a preclinical study, Gleevec (imatinib mesylate) in combination with LY294002 resulted in enhanced tumor growth inhibition compared to monotherapy in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT D816E, KIT Y570_L576del, and PTEN T321fs, which was established from a patient who did not respond to Gleevec (imatinib mesylate), Sutent (sunitinib), and Nexavar (sorafenib) (PMID: 29100343). | 29100343 |
| KIT Y570_L576del KIT D816E PTEN T321fs | gastrointestinal stromal tumor | sensitive | Regorafenib | Preclinical - Pdx | Actionable | In a preclinical study, Stivarga (regorafenib) inhibited Kit, Erk, and Mtor signaling, resulted in tumor growth inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT D816E, KIT Y570_L576del, and PTEN T321fs, which was established from a patient who did not respond to Gleevec (imatinib mesylate), Sutent (sunitinib), and Nexavar (sorafenib) (PMID: 29100343). | 29100343 |
| KIT Y570_L576del KIT D816E PTEN T321fs | gastrointestinal stromal tumor | resistant | Sunitinib | Preclinical - Pdx | Actionable | In a preclinical study, Sutent (sunitinib) demonstrated limited inhibition of Kit, Erk, and Mtor signaling and resulted in minimal (22.9%) tumor inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT D816E, KIT Y570_L576del, and PTEN T321fs, which was established from a patient who did not respond to Gleevec (imatinib mesylate), Sutent (sunitinib), and Nexavar (sorafenib) (PMID: 29100343). | 29100343 |
| KIT Y570_L576del KIT D816E PTEN T321fs | gastrointestinal stromal tumor | resistant | Imatinib | Preclinical - Pdx | Actionable | In a preclinical study, Gleevec (imatinib mesylate) did not inhibit Kit, Erk, or Mtor signaling and resulted in minimal tumor inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT D816E, KIT Y570_L576del, and PTEN T321fs, which was established from a patient who did not respond to Gleevec (imatinib mesylate), Sutent (sunitinib), and Nexavar (sorafenib) (PMID: 29100343). | 29100343 |
| PTEN loss | prostate cancer | predicted - sensitive | AR-mTOR-26 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AR-mTOR-26 treatment resulted in antitumor activity in prostate cancer xenograft models with PTEN loss (Cancer Res 2010;70(8 Suppl):Abstract nr 4484). | detail... |
| BRAF V600E/K PTEN loss | Advanced Solid Tumor | predicted - sensitive | PX-866 + Vemurafenib | Phase I | Actionable | In a Phase I trial, the combination therapy of PX-866 and Zelboraf (vemurafenib) demonstrated safety and resulted in an objective response in 28% (5/18) of advanced solid tumor patients harboring BRAF V600E or K, and of those five patients, 80% (4/5) also demonstrated loss of PTEN (PMID: 29051322). | 29051322 |
| PIK3CA P124L PTEN del | urinary bladder cancer | decreased response | Pictilisib | Preclinical - Cell culture | Actionable | In a preclinical study, Pictilisib (GDC-0941) demonstrated limited inhibition of Akt phosphorylation and growth in bladder cancer cells harboring PIK3CA P124L and PTEN deletion in culture (PMID: 28808038). | 28808038 |
| PTEN N48I | urinary bladder cancer | decreased response | Pictilisib | Preclinical - Cell culture | Actionable | In a preclinical study, Pictilisib (GDC-0941) demonstrated limited inhibition of Akt phosphorylation and growth in bladder cancer cells harboring PTEN N48I in culture (PMID: 28808038). | 28808038 |
| PIK3CA E542K PTEN loss | stomach cancer | unknown | Sirolimus | Phase 0 | Actionable | In a pilot clinical trial, Rapamune (sirolimus) demonstrated modest clinical activity in patients with PIK3CA-mutant gastric cancer (n=3) or hilar cholangiocarcinoma (n=1), including a gastric cancer patient harboring PIK3CA E542K and PTEN loss, with a 0% response rate, median progression-free survival of 1.9 months, and median overall survival of 3.6 months (PMID: 28685070). | 28685070 |
| PIK3CA E545K PTEN loss | stomach cancer | unknown | Sirolimus | Phase 0 | Actionable | In a pilot clinical trial, Rapamune (sirolimus) demonstrated modest clinical activity in patients with PIK3CA-mutant gastric cancer (n=3) or hilar cholangiocarcinoma (n=1), including 2 gastric cancer patients harboring PIK3CA E545K and PTEN loss, with a 0% response rate, median progression-free survival of 1.9 months, and median overall survival of 3.6 months (PMID: 28685070). | 28685070 |
| BRAF mut PTEN mut | melanoma | predicted - sensitive | ST-162 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, ST-162 resulted in tumor regression in a melanoma cell line xenograft model co-harboring mutations in BRAF and PTEN (PMID: 28775144). | 28775144 |
| PTEN R130Q | head and neck squamous cell carcinoma | predicted - sensitive | Carboplatin + Paclitaxel + Temsirolimus | Case Reports/Case Series | Actionable | In a Phase II trial, a patient with head and neck squamous cell carcinoma harboring PTEN R130Q demonstrated a partial response when treated with the combination of Torisel (temsirolimus), Paraplatin (carboplatin), and Taxol (paclitaxel) (PMID: 28961834). | 28961834 |
| PTEN loss | diffuse large B-cell lymphoma | predicted - sensitive | GSK2334470 + Idelalisib | Preclinical - Cell culture | Actionable | In a preclinical study, GSK2334470 partially restored sensitivity to Zydelig (idelalisib) in diffuse large B-cell lymphoma cells harboring PTEN loss that acquired resistance to Zydelig (idelalisib), resulting in increased apoptosis in culture (PMID: 28178345). | 28178345 |
| PTEN loss | diffuse large B-cell lymphoma | predicted - sensitive | Idelalisib + MK2206 | Preclinical - Cell culture | Actionable | In a preclinical study, MK2206 partially restored sensitivity to Zydelig (idelalisib) in diffuse large B-cell lymphoma cells harboring PTEN loss with acquired resistance to Zydelig (idelalisib), resulting in increased apoptosis in culture (PMID: 28178345). | 28178345 |
| PTEN loss | breast adenocarcinoma | sensitive | Gemcitabine + LY2780301 | Phase Ib/II | Actionable | In a Phase Ib trial, a breast adenocarcinoma patient harboring PTEN loss demonstrated a partial response when treated with a combination of LY2780301 and Gemzar (gemcitabine) (PMID: 28750271). | 28750271 |
| PTEN loss | head and neck squamous cell carcinoma | predicted - sensitive | Dactolisib | Preclinical - Cell culture | Actionable | In a preclinical study, BEZ235 resulted in antiproliferative activity in head and neck squamous cell carcinoma cells harboring PTEN loss in culture (PMID: 28446642). | 28446642 |
| PTEN loss | 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 PTEN loss in culture (PMID: 28446642). | 28446642 |
| PTEN dec exp | triple-receptor negative breast cancer | predicted - sensitive | Ipatasertib + Paclitaxel | Phase II | Actionable | In a Phase II trial, Ipatasertib (GDC-0068) in combination with Abraxane (paclitaxel) resulted in improved progression free survival (6.2 vs 3.7 months) compared to placebo in triple-receptor negative breast cancer patients with low Pten expression (PMID: 28800861; NCT02162719). | 28800861 |
| PTEN loss | colorectal cancer | sensitive | AZD8186 + Vistusertib | Phase I | Actionable | In a Phase I trial, the combination of AZD8186 and Vistusertib (AZD2014) resulted in a partial response in a patient with PTEN-deficient colorectal cancer (J Clin Oncol 35, 2017 (suppl; abstr 2570)). | detail... |
| BRAF V600E PTEN mut | melanoma | sensitive | ASN003 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a melanoma cell line xenograft model co-harboring BRAF V600E and a PTEN mutation demonstrated tumor growth inhibition when treated with ASN003 (Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B100). | detail... |
| BRAF V600E PTEN loss | melanoma | sensitive | GSK2636771 + unspecified PD-1 antibody | Preclinical | Actionable | In a preclinical study, treatment with the combination of GSK2636771 and a PD-1 antibody resulted in greater tumor infiltration of T-cells and tumor growth inhibition in mouse melanoma models expressing BRAF V600E with PTEN loss compared to either agent alone (PMID: 26645196). | 26645196 |
| PTEN loss | 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 partial response with 53% decrease of liver metastasis in a patients with head and neck squamous cell carcinoma harboring PTEN loss (Cancer Res April 15 2013 (73) (8 Supplement) LB-198). | detail... |
| PTEN loss TP53 loss | prostate cancer | sensitive | Capivasertib | Preclinical | Actionable | In a preclinical study, treatment with Truqap (capivasertib) improved overall survival and progression-free survival in mouse models of prostate cancer with inactivated PTEN and TP53 (PMID: 26910118). | 26910118 |
| PTEN loss | prostate cancer | sensitive | Capivasertib | Preclinical | Actionable | In a preclinical study, treatment with Truqap (capivasertib) decreased AKT phosphorylation and downstream signaling and reduced tumor burden in mouse models of PTEN-deficient prostate cancer, including both castration-naive and castration-resistant models (PMID: 26910118). | 26910118 |
| FGFR2 N550K PIK3CA I20M PIK3CA P539R PTEN R130Q PTEN T321fs | endometrial cancer | sensitive | Alpelisib + Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Truseltiq (infigratinib) and Alpelisib (BYL719) resulted in a synergistic effect, demonstrating inhibition of cell proliferation and induced cell death in an endometrial cancer cell line harboring FGFR2 N550K, PIK3CA I20M and P539R, and PTEN R130Q and T321fs*23 in culture (PMID: 28119489). | 28119489 |
| FGFR2 N550K PIK3CA I20M PIK3CA P539R PTEN R130Q PTEN T321fs | endometrial cancer | sensitive | Buparlisib + Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Truseltiq (infigratinib) and Buparlisib (BKM120) resulted in a synergistic effect, demonstrating inhibition of cell proliferation, decreased colony formation, and cell death in an endometrial cancer cell line harboring FGFR2 N550K, PIK3CA I20M and P539R, and PTEN R130Q and T321fs*23 in culture (PMID: 28119489). | 28119489 |
| FGFR2 N550K PIK3CA I20M PIK3CA P539R PTEN R130Q PTEN T321fs | endometrial cancer | sensitive | Infigratinib + Pictilisib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Truseltiq (infigratinib) and Pictilisib (GDC-0941) resulted in a synergistic effect, demonstrating inhibition of cell proliferation, decreased colony formation, and cell death in an endometrial cancer cell line harboring FGFR2 N550K, PIK3CA I20M and P539R, and PTEN R130Q and T321fs*23 in culture (PMID: 28119489). | 28119489 |
| PTEN loss | prostate cancer | sensitive | SF1126 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a glioblastoma cell line harboring PTEN loss (PMID: 24634413) was sensitive to SF1126, demonstrating a 76% decrease in tumor growth in cell line xenograft models (PMID: 18172313). | 18172313 24634413 |
| PTEN inact mut | glioblastoma | sensitive | SF1126 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a glioblastoma cell line harboring a PTEN inactivating mutation (PMID: 24634413) was sensitive to SF1126, demonstrating inhibition of tumor growth in cell line xenograft models (PMID: 18172313). | 18172313 24634413 |
| PTEN loss | breast adenocarcinoma | sensitive | Voxtalisib | Preclinical - Cell culture | Actionable | In a preclinical study, a breast adenocarcinoma cell line harboring PTEN loss was sensitive to XL765 (SAR245409), demonstrating inhibition of cell proliferation in culture (PMID: 24634413). | 24634413 |
| PTEN inact mut | glioblastoma | sensitive | Voxtalisib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a glioblastoma cell line harboring a PTEN inactivating mutation 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 |
| PTEN loss | prostate cancer | sensitive | Voxtalisib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a prostate cancer cell line with PTEN loss was sensitive to XL765 (SAR245409) treatment, demonstrating inhibition of the PI3K pathway and decreased colony formation in culture, and inhibition of tumor growth and reduced tumor vascularization in cell line xenograft models (PMID: 24634413). | 24634413 |
| PTEN loss | glioblastoma | sensitive | GDC-0084 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, two PTEN-deficient glioblastoma cell line xenograft models were sensitive to GDC-0084 treatment, resulting in decreased tumor volumes by 70% and 40%, and inhibition of PI3K pathway signaling (PMID: 27638506). | 27638506 |
| PTEN loss | acute lymphoblastic leukemia | sensitive | BGT226 | Preclinical - Cell culture | Actionable | In a preclinical study, BGT226 treatment in PTEN-deficient acute lymphoblastic leukemia cells resulted in inhibition of PI3K/Akt signaling and apoptotic activity in culture (PMID: 23705826). | 23705826 |
| PTEN loss | Advanced Solid Tumor | no benefit | Everolimus | Phase II | Actionable | In a Phase II trial, Afinitor (everolimus) treatment in patients with advanced solid tumors harboring PTEN loss did not reach its primary endpoint, resulting in only stable disease or progressive disease (PMID: 28330462). | 28330462 |
| PIK3CA wild-type PTEN loss | breast cancer | sensitive | Selumetinib + Torkinib | Preclinical - Cell culture | Actionable | In a preclinical study, breast cancer cells harboring PIK3CA wild-type and PTEN loss demonstrated sensitivity to the combination treatment of Torkinib (PP242) and Selumetinib (AZD6244) in culture (PMID: 21358673). | 21358673 |
| PIK3CA wild-type PTEN loss | breast cancer | sensitive | Torkinib + U0126 | Preclinical - Cell culture | Actionable | In a preclinical study, breast cancer cells harboring PIK3CA wild-type and PTEN loss demonstrated sensitivity to the combination treatment of Torkinib (PP242) and U0126 in culture (PMID: 21358673). | 21358673 |
| PIK3CA wild-type PTEN loss | breast cancer | no benefit | Everolimus + Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, breast cancer cells harboring PIK3CA wild-type and PTEN loss did not demonstrate any benefit when treated with a combination of Afinitor (everolimus) and Selumetinib (AZD6244) (PMID: 21358673). | 21358673 |
| PIK3CA wild-type PTEN loss | breast cancer | no benefit | Everolimus + U0126 | Preclinical - Cell culture | Actionable | In a preclinical study, breast cancer cells harboring PIK3CA wild-type and PTEN loss did not demonstrate any benefit when treated with a combination of Afinitor (everolimus) and U0126 (PMID: 21358673). | 21358673 |
| PTEN loss | breast cancer | resistant | Torkinib | Preclinical - Cell culture | Actionable | In a preclinical study, breast cancer cell lines with PTEN loss demonstrated resistance to Torkinib (PP242) in culture (PMID: 21358673). | 21358673 |
| PTEN loss | breast cancer | resistant | Everolimus | Preclinical - Cell culture | Actionable | In a preclinical study, 10/12 breast cancer cell lines with PTEN loss demonstrated resistance to Afinitor (everolimus) in culture (PMID: 21358673). | 21358673 |
| PIK3CA act mut PTEN wild-type | breast cancer | sensitive | Torkinib | Preclinical - Cell culture | Actionable | In a preclinical study, 9/9 breast cancer cell lines harboring a PIK3CA activating mutation and PTEN wild-type demonstrated sensitivity to treatment with Torkinib (PP242) in culture, resulting in decreased cell viability (PMID: 21358673). | 21358673 |
| PIK3CA act mut PTEN wild-type | breast cancer | sensitive | Everolimus | Preclinical - Cell culture | Actionable | In a preclinical study, 8/9 breast cancer cell lines harboring a PIK3CA activating mutation and PTEN wild-type demonstrated sensitivity to treatment with Afinitor (everolimus) in culture, resulting in decreased cell viability (PMID: 21358673). | 21358673 |
| PTEN V275* | triple-receptor negative breast cancer | sensitive | DHM25 | Preclinical - Cell culture | Actionable | In a preclinical study, DHM25 increased cell death and decreased migration of a triple-negative breast cancer cell line harboring PTEN V275* in culture (PMID: 26237138). | 26237138 |
| PTEN A72fs | triple-receptor negative breast cancer | sensitive | DHM25 | Preclinical - Cell culture | Actionable | In a preclinical study, DHM25 increased cell death in a triple-negative breast cancer cell line harboring PTEN A72fs*5 in culture (PMID: 26237138). | 26237138 |
| PTEN L108R | breast cancer | sensitive | DHM25 | Preclinical - Cell culture | Actionable | In a preclinical study, DHM25 increased cell death in a breast cancer cell line harboring PTEN L108R in culture (PMID: 26237138). | 26237138 |
| PTEN loss | transitional cell carcinoma | predicted - resistant | Everolimus | Case Reports/Case Series | Actionable | In a Phase II trial, 57% (8/14) of transitional cell carcinoma patients that demonstrated uncontrolled disease after treatment with Afinitor (everolimus) harbored PTEN loss, while 0% (0/6) of patients with controlled disease demonstrated evidence of PTEN loss (PMID: 22473592). | 22473592 |
| PTEN mutant | melanoma | sensitive | BI-69A11 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, BI-69A11 resulted in antitumor activity in a melanoma cell line harboring a PTEN mutation, including induction of cell death in culture, and in xenograft models, tumor growth inhibition and tumor regression (PMID: 19175524). | 19175524 |
| PTEN loss | triple-receptor negative breast cancer | sensitive | M2698 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a triple-receptor negative breast cancer xenograft model harboring PTEN loss was sensitive to M2698 (MSC2363318A), demonstrating inhibition of tumor growth and tumor regression (PMID: 27186432). | 27186432 |
| PIK3CA R93W PIK3CA D350G PTEN R130G | endometrial cancer | sensitive | Miransertib | Preclinical - Pdx | Actionable | In a preclinical study, a patient-derived xenograft (PDX) model of endometrial cancer harboring PIK3CA D350G, PIK3CA R93W, and PTEN R130G was sensitive to Miransertib (ARQ092), demonstrating greater than 90% inhibition of tumor growth (PMID: 26469692). | 26469692 |
| PTEN loss | castration-resistant prostate carcinoma | sensitive | Abiraterone + Ipatasertib | Phase II | Actionable | In a Phase II trial, the combination of Ipatasertib (GDC-0068) and Zytiga (abiraterone) resulted in a better progression-free survival in metastatic castration resistant prostate cancer patients with PTEN loss (by IHC) when compared to placebo combined with Zytiga (PMID: 30037818; NCT01485861). | 30037818 detail... |
| PTEN loss | castration-resistant prostate carcinoma | sensitive | Abiraterone + Ipatasertib | Phase III | Actionable | In a Phase III trial, Ipatasertib (GDC-0068) combined with Zytiga (abiraterone) significantly improved median radiographical progression-free survival (PFS) (18.5 vs 16.5 mo, HR 0.77, p=0.034) in patients with metastatic castration resistant prostate cancer harboring PTEN loss (by IHC) when compared to placebo combined with Zytiga, median PFS was not improved (19.2 vs 16.6 mo, HR 0.84, p=0.043) in the intent-to-treat population (PMID: 34246347; NCT03072238). | 34246347 |
| PIK3CA H1047R PTEN loss | triple-receptor negative breast cancer | predicted - sensitive | ABT-737 + Sapanisertib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, ABT-737 and Sapanisertib (MLN0128) combination treatment resulted in inhibition of tumor growth in cell line xenograft models of triple-receptor negative breast cancer harboring PIK3CA H1047R and PTEN loss (PMID: 27974663). | 27974663 |
| PIK3CA H1047R PTEN loss | triple-receptor negative breast cancer | predicted - sensitive | ABT-737 + Dactolisib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, ABT-737 and BEZ235 combination treatment resulted in tumor regression in cell line xenograft models of triple-receptor negative breast cancer harboring PIK3CA H1047R and PTEN loss (PMID: 27974663). | 27974663 |
| PIK3CA E542K PTEN loss | breast cancer | predicted - sensitive | Dactolisib + WEHI-539 | Preclinical - Cell culture | Actionable | In a preclinical study, inhibition of Pi3k signaling by BEZ235 sensitized breast cancer cell lines harboring PIK3CA E542K and PTEN loss to WEHI-539 in culture (PMID: 27974663). | 27974663 |
| PIK3CA H1047R PTEN loss | breast cancer | predicted - sensitive | Dactolisib + WEHI-539 | Preclinical - Cell culture | Actionable | In a preclinical study, inhibition of Pi3k signaling by BEZ235 sensitized breast cancer cell lines harboring PIK3CA H1047R and PTEN loss to WEHI-539 in culture (PMID: 27974663). | 27974663 |
| PIK3CA H1047R PTEN loss | breast cancer | no benefit | Dactolisib + Venetoclax | Preclinical - Cell culture | Actionable | In a preclinical study, inhibition of Pi3k signaling by BEZ235 did not sensitize breast cancer cell lines harboring PIK3CA H1047R and PTEN loss to Venclexta (venetoclax) in culture (PMID: 27974663). | 27974663 |
| PTEN mut TP53 mut | glioblastoma | sensitive | Navitoclax + ONC201 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of ONC201 (TIC10) and Navitoclax (ABT-263) increased apoptosis and worked synergistically to inhibit proliferation of a glioblastoma cell line harboring mutations in PTEN and TP53 in culture (PMID: 26474387). | 26474387 |
| PTEN del | breast cancer | sensitive | CUDC-907 | Preclinical - Cell culture | Actionable | In a preclinical study, CUDC-907 inhibited growth of breast cancer cells lines harboring Pten mutations and/or deletions (PMID: 22693356). | 22693356 |
| PTEN mutant | breast cancer | sensitive | CUDC-907 | Preclinical - Cell culture | Actionable | In a preclinical study, CUDC-907 inhibited growth of breast cancer cells lines harboring Pten mutations and/or deletions (PMID: 22693356). | 22693356 |
| PTEN negative | lung squamous cell carcinoma | sensitive | Buparlisib | Phase II | Actionable | In a Phase II trial, one patient with Pten negative squamous NSCLC had a partial response to Buparlisib (BKM120) however, stage 2 of the study was not initiated due to failure of meeting overall stage 1 response endpoints (PMID: 26098748). | 26098748 |
| PTEN loss | Advanced Solid Tumor | sensitive | Capivasertib | Preclinical - Cell culture | Actionable | In a preclinical study, Truqap (capivasertib) inhibited growth of various solid tumor cell culture models with loss of Pten (PMID: 22294718). | 22294718 |
| PTEN inact mut | Advanced Solid Tumor | sensitive | Capivasertib | Preclinical - Cell culture | Actionable | In a preclinical study, Truqap (capivasertib) inhibited growth of various solid tumor cell culture models with inactivating Pten mutations (PMID: 22294718). | 22294718 |
| PTEN loss | renal carcinoma | sensitive | Capivasertib | Preclinical - Pdx | Actionable | In a preclinical study, Truqap (capivasertib) inhibited growth of renal cancer Pdx models with Pten loss (PMID: 22294718). | 22294718 |
| PTEN loss | prostate cancer | sensitive | Ipatasertib | Case Reports/Case Series | Actionable | In a Phase I trial, a patient with castration resistant prostate cancer harboring a loss of PTEN demonstrated an improved prostate specific antigen when treated with Ipatasertib (GDC-0068) (PMID: 27872130). | 27872130 |
| PIK3CA R88L PIK3CA E453del PIK3CA T1052K PTEN loss PTEN mut | endometrial carcinoma | sensitive | Copanlisib | Phase I | Actionable | In a Phase I clinical trial, an endometrial carcinoma patient harboring PIK3CA T1052K, R88L, and E453del, as well as a PTEN mutation and loss of PTEN protein expression demonstrated a complete response to treatment with Aliqopa (copanlisib) (PMID: 27672108). | 27672108 |
| PTEN loss | prostate cancer | no benefit | CX-5461 | Preclinical | Actionable | In a preclinical study, CX-5461 treatment did not result in histological change in PTEN deficient transgenic animal model of prostate cancer (PMID: 27486174). | 27486174 |
| PTEN loss | prostate cancer | predicted - sensitive | CX-5461 + CX-6258 | Preclinical | Actionable | In a preclinical study, CX-6258 and CX-5461 combination treatment resulted in decreased tumor burden in PTEN deficient transgenic animal model of prostate cancer (PMID: 27486174). | 27486174 |
| PTEN loss | prostate cancer | predicted - sensitive | CX-6258 | Preclinical | Actionable | In a preclinical study, CX-6258 treatment resulted in decreased carcinoma in situ in PTEN deficient transgenic animal model of prostate cancer (PMID: 27486174). | 27486174 |
| APC inact mut PTEN inact mut | colorectal cancer | no benefit | Binimetinib + Dactolisib | Preclinical | Actionable | In a preclinical study, combination of BEZ235 and Binimetinib (MEK162) did not improve survival compared to single agent in transgenic animal models of colorectal cancer driven by APC and PTEN inactivation (PMID: 26206338). | 26206338 |
| APC inact mut PTEN inact mut | colorectal cancer | no benefit | Binimetinib | Preclinical | Actionable | In a preclinical study, Binimetinib (MEK162) reduced proliferation in tumors acutely but did not improve survival in transgenic animal models of colorectal cancer driven by APC and PTEN inactivation (PMID: 26206338). | 26206338 |
| APC inact mut PTEN inact mut | colorectal cancer | sensitive | Dactolisib | Preclinical | Actionable | In a preclinical study, BEZ235 inhibited PI3K/mTOR signaling in tumors and increased survival in transgenic animal models of colorectal cancer driven by APC and PTEN inactivation (PMID: 26206338). | 26206338 |
| PTEN del | prostate cancer | sensitive | Ipatasertib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, prostate cancer cell line xenograft models with PTEN deletion demonstrated sensitivity to treatment with Ipatasertib (GDC-0068), resulting in inhibition of tumor growth (PMID: 24141624). | 24141624 |
| PTEN inact mut | kidney cancer | sensitive | LY3023414 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, LY3023414 inhibited proliferation of renal cancer cells harboring PTEN inactivating mutation in culture, resulted in tumor growth inhibition in cell line xenograft models (PMID: 27439478). | 27439478 |
| PTEN loss | glioblastoma | sensitive | LY3023414 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, LY3023414 inhibited Pi3k/mTor signaling and proliferation in PTEN deficient glioblastoma cells in culture, and resulted in tumor growth inhibition in cell line xenograft models (PMID: 27439478). | 27439478 |
| PTEN loss | breast cancer | resistant | Alpelisib | Preclinical - Cell culture | Actionable | In a preclinical study, breast cancer cells harboring PTEN loss demonstrated resistance to Alpelisib (BYL719) in culture (PMID: 27604488). | 27604488 |
| PTEN C136Y | breast cancer | resistant | Alpelisib | Preclinical - Cell culture | Actionable | In a preclinical study, breast cancer cells harboring PTEN C136Y demonstrated resistance to Alpelisib (BYL719) in culture (PMID: 27604488). | 27604488 |
| PIK3CA H1047R PTEN E307K | breast cancer | sensitive | BAY1125976 | Preclinical - Cell culture | Actionable | In a preclinical study, BAY1125976 inhibited proliferation of a breast cancer cell line harboring PIK3CA H1047R and PTEN E307K in culture (PMID: 27699769). | 27699769 |
| PTEN T319fs | breast cancer | sensitive | BAY1125976 | Preclinical - Cell culture | Actionable | In a preclinical study, BAY1125976 inhibited proliferation of a breast cancer cell line harboring PTEN T319fs*1 in culture (PMID: 27699769). | 27699769 |
| PTEN L108R | breast cancer | sensitive | BAY1125976 | Preclinical - Cell culture | Actionable | In a preclinical study, BAY1125976 inhibited proliferation of a breast cancer cell line harboring PTEN L108R in culture (PMID: 27699769). | 27699769 |
| PTEN loss | breast cancer | sensitive | OSI-027 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, OSI-027 induced tumor regression in PTEN-null breast cancer cell line xenograft models (PMID: 21673091). | 21673091 |
| PTEN loss | ovarian cancer | sensitive | OSI-027 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, OSI-027 inhibited tumor growth in PTEN-null ovarian cancer cell line xenograft models (PMID: 21673091). | 21673091 |
| PTEN mutant | breast cancer | predicted - sensitive | MS417 + Pictilisib | Preclinical - Cell culture | Actionable | In a preclinical study, Pictilisib (GDC-0941) and MS417 in combination resulted in improved growth inhibition and increased cell death compared to either agent alone in a PTEN-mutant breast cancer cell line in culture (PMID: 26058079). | 26058079 |
| PTEN loss | glioblastoma | no benefit | BLZ945 | Preclinical | Actionable | In a preclinical study, BLZ945 resulted in limited benefit in transgenic mouse models of glioblastoma harboring a loss of PTEN (PMID: 27199435). | 27199435 |
| BRAF V600E PTEN loss TP53 wild-type | colorectal cancer | sensitive | PD-0325901 + Sapanisertib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 synergistically inhibited Erk and PI3K signaling and proliferation, induced apoptosis in TP53-wild-type colorectal cancer cells harboring BRAF V600E and PTEN loss in culture and in cell line xenograft models (PMID: 26272063). | 26272063 |
| PTEN inact mut | estrogen-receptor positive breast cancer | sensitive | Fulvestrant + Pictilisib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Faslodex (fulvestrant) and PIctilisib (GDC-0941) resulted in decreased cell viability and increased apoptotic activity in PTEN deficient estrogen-receptor (ER) positive breast cancer cells in culture (PMID: 26733612). | 26733612 |
| PTEN inact mut | estrogen-receptor positive breast cancer | sensitive | Pictilisib | Preclinical - Cell culture | Actionable | In a preclinical study, a PTEN deficient estrogen-receptor (ER) positive breast cancer cell line demonstrated increased sensitivity to treatment in culture when Pictilisib (GDC-0941) was given at a higher dose for a shorter duration, resulting in inhibition of cell growth (PMID: 26733612). | 26733612 |
| PTEN loss | prostate cancer | sensitive | Acalisib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Acalisib (GS-9820) resulted in tumor growth inhibition in xenograft models of prostate cancer with PTEN deficiency (Mol Cancer Ther 2009;8(12 Suppl):B136). | detail... |
| PTEN R130* | thyroid gland follicular carcinoma | sensitive | MK2206 | Preclinical - Cell culture | Actionable | In a preclinical study, MK2206 inhibited AKT activation, proliferation, and growth of thyroid cancer cell lines with PI3K/AKT pathway alterations in culture, including an follicular thyroid cancer cell line harboring PTEN R130* and loss of one PTEN allele (PMID: 21289267). | 21289267 |
| BRAF V600X PTEN neg | melanoma | sensitive | Uprosertib | Preclinical - Cell culture | Actionable | In a preclinical study, lack of PTEN expression was associated with increased sensitivity to GSK2141795 in BRAF V600-mutant melanoma cell lines in culture (PMID: 24265152). | 24265152 |
| PIK3CA mut PTEN loss | prostate cancer | sensitive | PKI-179 | Preclinical - Cell culture | Actionable | In a preclinical study, PKI-179 inhibited growth of prostate cancer cells harboring PIK3CA mutations and PTEN loss in culture (PMID: 20797855). | 20797855 |
| BRAF V600E PTEN loss | melanoma | sensitive | GDC0879 + Pictilisib | Preclinical - Cell culture | Actionable | In a preclinical study, GDC0879 and Pictilisib (GDC-0941) synergistically inhibited survival of melanoma cell lines harboring BRAF V600E and PTEN loss in cell culture (PMID: 19276360). | 19276360 |
| BRAF mut PTEN loss | melanoma | sensitive | SAR260301 + Selumetinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, SAR260301 and Selumetinib (AZD6244) synergistically inhibited proliferation of PTEN deficient melanoma cells harboring BRAF mutations in culture and suppressed tumor growth in cell line xenograft models (PMID: 27196754). | 27196754 |
| BRAF mut PTEN loss | melanoma | sensitive | SAR260301 + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, SAR260301 and Zelboraf (vemurafenib) synergistically inhibited proliferation of PTEN deficient melanoma cells harboring BRAF mutations in culture and suppressed tumor growth in cell line xenograft models (PMID: 27196754). | 27196754 |
| PTEN loss | prostate carcinoma | decreased response | SAR260301 | Preclinical - Cell line xenograft | Actionable | In a precliinical study, PTEN deficient prostate carcinoma cells demonstrated reduced response to SAR260301 in cell culture and in cell line xenograft models (PMID: 27196754). | 27196754 |
| BRAF mut PTEN loss | melanoma | sensitive | SAR260301 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, SAR260301 inhibited proliferation of PTEN deficient melanoma cells harboring BRAF mutations in culture and suppressed tumor growth in cell line xenograft models (PMID: 27196754). | 27196754 |
| PTEN loss | glioblastoma | resistant | A66 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, A66 did not inhibit tumor growth in a PTEN-null cell line xenograft model of glioblastoma (PMID: 21668414). | 21668414 |
| PTEN dec exp | Advanced Solid Tumor | predicted - sensitive | Pemetrexed Disodium + Sorafenib | Phase I | Actionable | In a Phase I clinical trial, low Pten expression or lack of Pten expression was associated with better response to treatment with the combination of Alimta (pemetrexed) and Nexavar (sorafenib) in patients with advanced solid tumors (PMID: 27213589). | 27213589 |
| BRAF V600X PTEN H93D | melanoma | predicted - sensitive | Vemurafenib | Clinical Study - Cohort | Actionable | In a clinical study, a melanoma patient harboring a BRAF V600 mutation and PTEN H93D treated with Zelboraf (vemurafenib) for 66 weeks demonstrated a partial response (PMID: 24265153). | 24265153 |
| BRAF V600E PTEN loss | melanoma | sensitive | Pictilisib + PLX4720 | Preclinical | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and PTEN loss demonstrated sensitivity when treated with a combination of Pictilisib (GDC-0941) and PLX4720, resulting in decreased cell proliferation in culture (PMID: 24265153). | 24265153 |
| PTEN loss | melanoma | sensitive | DETD-35 + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, DETD-35 and Zelboraf (vemurafenib) combination treatment resulted in further reduction of tumor size in cell line xenograft models of Zelboraf (vemurafenib)-resistant melanoma harboring PTEN loss when compared to single agent treatment (PMID: 27048951). | 27048951 |
| PTEN loss | melanoma | sensitive | DETD-35 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, DETD-35 treatment resulted in reduced tumor size in cell line xenograft models of Zelboraf (vemurafenib)-resistant melanoma harboring PTEN loss (PMID: 27048951). | 27048951 |
| PTEN inact mut | prostate adenocarcinoma | sensitive | Paclitaxel + XL147 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of XL147 and Taxol (paclitaxel) inhibited tumor growth and angiogenesis in xenograft models of a human prostate adenocarcinoma cell line harboring an inactivating mutation in PTEN, with increased efficacy compared to either agent alone (PMID: 25637314). | 25637314 |
| PTEN inact mut | prostate adenocarcinoma | sensitive | XL147 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, XL147 inhibited PI3K signaling, growth, and migration of a human prostate adenocarcinoma cell line harboring a PTEN inactivating mutation in culture, and inhibited tumor growth and vascularization in xenograft models (PMID: 25637314). | 25637314 |
| BRAF V600D PTEN loss | melanoma | sensitive | XL147 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, XL147 inhibited tumor growth in xenograft models of a PTEN-deficient human melanoma cell line harboring BRAF V600D (PMID: 25637314). | 25637314 |
| BRAF V600E PTEN loss | melanoma | sensitive | XL147 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, XL147 inhibited tumor growth in xenograft models of a PTEN-deficient human melanoma cell line harboring BRAF V600E (PMID: 25637314). | 25637314 |
| PTEN V54fs | glioblastoma | sensitive | XL147 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, XL147 inhibited tumor growth in xenograft models of a human glioblastoma cell line harboring PTEN V54fs (PMID: 25637314). | 25637314 |
| BRAF mut PTEN inact mut | melanoma | sensitive | Encorafenib + GSK2636771 + unspecified IGF-1R antibody | Preclinical - Cell line xenograft | Actionable | In a preclinical study, combination treatment consisting of GSK2636771, Encorafenib (LGX818), and a figitumumab-like antibody inhibited tumor growth in xenograft models of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | Encorafenib + unspecified IGF-1R antibody | Preclinical | Actionable | In a preclinical study, combination treatment consists of Encorafenib (LGX818) and a figitumumab-like antibody inhibited tumor growth in xenograft models of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | GSK2636771 + unspecified IGF-1R antibody | Preclinical - Cell line xenograft | Actionable | In a preclinical study, combination treatment consisting of GSK2636771 and a figitumumab-like antibody inhibited tumor growth in xenograft models of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | Alpelisib + Encorafenib + GSK2636771 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of GSK2636771, Encorafenib (LGX818), and Alpelisib (BYL719) efficiently inhibited tumor growth in xenograft models of a human melanoma cell line harboring BRAF mutations and PTEN inactivating mutations (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | Alpelisib + AZD6482 + Binimetinib + Encorafenib | Preclinical | Actionable | In a preclinical study, combination treatment consisting of AZD6482, Binimetinib (MEK162), Encorafenib (LGX818), and Alpelisib (BYL719) efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | AZD6482 + Binimetinib + Encorafenib + NVP-AEW541 | Preclinical | Actionable | In a preclinical study, combination treatment consists of AZD6482, Binimetinib (MEK162), Encorafenib (LGX818), and NVP-AEW541 efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | AZD6482 + Binimetinib + NVP-AEW541 | Preclinical | Actionable | In a preclinical study, combination treatment consists of AZD6482, Binimetinib (MEK162), and NVP-AEW541 efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | Alpelisib + AZD6482 + Binimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination treatment consisting of AZD6482, Binimetinib (MEK162), and Alpelisib (BYL719) efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | AZD6482 + Encorafenib + NVP-AEW541 | Preclinical | Actionable | In a preclinical study, combination treatment consists of AZD6482, Encorafenib (LGX818), and NVP-AEW541 efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | Alpelisib + AZD6482 + Encorafenib | Preclinical | Actionable | In a preclinical study, combination treatment consisting of AZD6482, Encorafenib (LGX818), and Alpelisib (BYL719) efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN wild-type | melanoma | no benefit | Encorafenib + GSK2636771 | Preclinical | Actionable | In a preclinical study, GSK2636771 and Encorafenib (LGX818) combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN wild-type | melanoma | no benefit | AZD6482 + Encorafenib | Preclinical | Actionable | In a preclinical study, AZD6482 and Encorafenib (LGX818) combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN wild-type | melanoma | no benefit | Binimetinib + GSK2636771 | Preclinical | Actionable | In a preclinical study, GSK2636771 and Binimetinib (MEK162) combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN wild-type | melanoma | no benefit | AZD6482 + Binimetinib | Preclinical | Actionable | In a preclinical study, AZD6482 and Binimetinib (MEK162) combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | no benefit | Alpelisib + Binimetinib | Preclinical | Actionable | In a preclinical study, Alpelisib (BYL719) and Binimetinib (MEK162) combination treatment did not enhance growth inhibition compared to single agent in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | Binimetinib + GSK2636771 | Preclinical | Actionable | In a preclinical study, GSK2636771 and Binimetinib (MEK162) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | AZD6482 + Binimetinib | Preclinical | Actionable | In a preclinical study, AZD6482 and Binimetinib (MEK162) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | Binimetinib + Pictilisib | Preclinical | Actionable | In a preclinical study, Pictilisib (GDC-0941) and Binimetinib (MEK162) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | no benefit | Alpelisib + Encorafenib | Preclinical | Actionable | In a preclinical study, Alpelisib (BYL719) and Encorafenib (LGX818) combination treatment did not enhance growth inhibition in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | Encorafenib + GSK2636771 | Preclinical | Actionable | In a preclinical study, GSK2636771 and Encorafenib (LGX818) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | AZD6482 + Encorafenib | Preclinical | Actionable | In a preclinical study, AZD6482 and Encorafenib (LGX818) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | Encorafenib + Pictilisib | Preclinical | Actionable | In a preclinical study, Pictilisib (GDC-0941) and Encorafenib (LGX818) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN wild-type | melanoma | no benefit | GSK2636771 + NVP-AEW541 | Preclinical | Actionable | In a preclinical study, GSK2636771 and NVP-AEW541 combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN wild-type | melanoma | no benefit | AZD6482 + NVP-AEW541 | Preclinical | Actionable | In a preclinical study, AZD6482 and NVP-AEW541 combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | no benefit | Alpelisib + NVP-AEW541 | Preclinical | Actionable | In a preclinical study, Alpelisib (BYL719) and NVP-AEW541 combination treatment did not enhance growth inhibition compared to single agent in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | NVP-AEW541 + Pictilisib | Preclinical | Actionable | In a preclinical study, Pictilisib (GDC-0941) and NVP-AEW541 synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | GSK2636771 + NVP-AEW541 | Preclinical | Actionable | In a preclinical study, GSK2636771 and NVP-AEW541 synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | AZD6482 + NVP-AEW541 | Preclinical | Actionable | In a preclinical study, AZD6482 and NVP-AEW541 synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | Alpelisib + GSK2636771 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of GSK2636771 and Alpelisib (BYL719) synergized to inhibit proliferation of human melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture, and inhibited tumor growth in xenograft models of one cell line harboring these mutations (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | Alpelisib + AZD6482 | Preclinical | Actionable | In a preclinical study, AZD6482 and Alpelisib (BYL719) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | decreased response | Alpelisib | Preclinical | Actionable | In a preclincal study, melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations were less sensitive to Alpelisib (BYL719)-induced growth inhibition in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | Pictilisib | Preclinical | Actionable | In a preclincal study, Pictilisib (GDC-0941) inhibited Akt activation and proliferation in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | TGX-221 | Preclinical | Actionable | In a preclincal study, TGX-221 inhibited Akt activation and proliferation in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | AZD6482 | Preclinical | Actionable | In a preclincal study, AZD6482 inhibited Akt activation and proliferation in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| PTEN loss | ovarian mucinous neoplasm | no benefit | KX2-391 + Oxaliplatin | Preclinical | Actionable | In a preclinical study, KX2-391 and Eloxatin (oxaliplatin) combination treatment did not show improved tumor suppression in xenograft models of ovarian mucinous carcinoma harboring PTEN loss when compared to single agent treatment (PMID: 24100628). | 24100628 |
| PTEN G129R | ovarian mucinous neoplasm | decreased response | KX2-391 | Preclinical | Actionable | In a preclincal study, mucinous ovarian carcinoma cell lines over-expressing PTEN G129R were less sensitive to KX2-391 induced growth inhibition in culture and tumor suppression in xenograft models (PMID: 24100628). | 24100628 |
| PTEN loss | ovarian mucinous neoplasm | decreased response | KX2-391 | Preclinical | Actionable | In a preclincal study, mucinous ovarian carcinoma cell lines harboring PTEN loss were less sensitive to KX2-391 induced growth inhibition in culture and tumor suppression in xenograft models (PMID: 24100628). | 24100628 |
| PTEN wild-type | ovarian mucinous neoplasm | sensitive | KX2-391 + Oxaliplatin | Preclinical | Actionable | In a preclinical study, KX2-391 and Eloxatin (oxaliplatin) synergistically inhibited survival of PTEN wild-type mucinous ovarian carcinoma cell lines in culture, and reduced tumor growth in xenograft models (PMID: 24100628). | 24100628 |
| PTEN wild-type | ovarian mucinous neoplasm | sensitive | KX2-391 | Preclinical | Actionable | In a preclinical study, KX2-391 inhibited survival of PTEN wild-type mucinous ovarian carcinoma cell lines in culture, and reduced tumor growth in xenograft models (PMID: 24100628). | 24100628 |
| PTEN del | head and neck squamous cell carcinoma | resistant | Taselisib | Preclinical | Actionable | In a preclinical study, head and neck squamous cell carcinoma cells homozygous for PTEN deletion were resistant to Taselisib (GDC-0032) in culture (PMID: 26589432). | 26589432 |
| PTEN loss RB1 loss | triple-receptor negative breast cancer | resistant | Palbociclib | Preclinical | Actionable | In a preclinical study, a triple-receptor negative breast cancer line harboring PTEN and RB1 loss was resistant to Ibrance (palbociclib) induced growth inhibition in culture (PMID: 27020857). | 27020857 |
| PTEN loss RB1 loss | triple-receptor negative breast cancer | resistant | Pictilisib | Preclinical | Actionable | In a preclinical study, a triple-receptor negative breast cancer line harboring PTEN and RB1 loss was resistant to Pictilisib (GDC-0941) induced growth inhibition in culture (PMID: 27020857). | 27020857 |
| PTEN loss RB1 loss | triple-receptor negative breast cancer | no benefit | Palbociclib + Pictilisib | Preclinical | Actionable | In a preclinical study, the combination of Ibrance (palbociclib) and Pictilisib (GDC-0941) did not improve growth inhibition compared to single drug treatment in triple-receptor negative breast cancer cell lines harboring PTEN and RB1 loss in culture (PMID: 27020857). | 27020857 |
| PIK3CA act mut PTEN dec exp | renal cell carcinoma | no benefit | Everolimus | Case Reports/Case Series | Actionable | In a retrospective analysis from a Phase II clinical trial, patients with metastatic renal cell carcinoma treated with Afinitor (everolimus) had no difference in progression-free survival when stratified by the presence (n=21) or absence (n=17) of PIK3CA activating mutations (PMID: 26951309). | 26951309 |
| PTEN dec exp | renal cell carcinoma | no benefit | Everolimus | Case Reports/Case Series | Actionable | In a retrospective analysis from a Phase II clinical trial, patients with metastatic renal cell carcinoma treated with Afinitor (everolimus) had no difference in progression-free survival when stratified by high expression (n=17) and low expression (n=21) of Pten (PMID: 26951309). | 26951309 |
| PIK3CA act mut PTEN dec exp | renal cell carcinoma | no benefit | Apitolisib | Case Reports/Case Series | Actionable | In a retrospective analysis from a Phase II clinical trial, patients with metastatic renal cell carcinoma treated with Apitolisib (GDC-0980) had no difference in progression-free survival when stratified by the presence (n=21) or absence (n=15) of PIK3CA activating mutation and/or decreased Pten expression (PMID: 26951309). | 26951309 |
| PTEN dec exp | renal cell carcinoma | no benefit | Apitolisib | Case Reports/Case Series | Actionable | In a retrospective analysis from a Phase II clinical trial, patients with metastatic renal cell carcinoma treated with Apitolisib (GDC-0980) had no difference in progression-free survival when stratified by high expression (n=17) and low expression (n=19) of Pten (PMID: 26951309). | 26951309 |
| BRAF mut PTEN wild-type | melanoma | sensitive | E6201 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, E6201 resulted in a cytocidal response in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture and inhibited tumor growth in cell line xenograft models (PMID: 23039341). | 23039341 |
| BRAF mut PTEN mut | melanoma | decreased response | E6201 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, E6201 resulted in a cytostatic response in melanoma cell lines harboring both BRAF and PTEN mutations in culture and only inhibited tumor growth at very high doses in cell line xenograft models (PMID: 23039341). | 23039341 |
| PTEN mutant | uterine cancer | sensitive | GSK2256098 + Topotecan | Preclinical | Actionable | In a preclinical study, uterine cancer cells harboring a PTEN mutation were more sensitive to the combination of GSK2256098 and Hycamtin (topotecan) than uterine cancer cells wild-type for PTEN, resulting in decreased tumor growth in culture and in mouse models (PMID: 25833835). | 25833835 |
| PTEN mutant | uterine cancer | sensitive | GSK2256098 + Paclitaxel | Preclinical | Actionable | In a preclinical study, uterine cancer cells harboring a PTEN mutation were more sensitive to the combination of GSK2256098 and Taxol (paclitaxel) than uterine cancer cells wild-type for PTEN, resulting in decreased tumor growth in culture and in mouse models (PMID: 25833835). | 25833835 |
| PTEN loss | sarcoma | sensitive | YU238259 | Preclinical | Actionable | In a preclinical study, YU238259 demonstrated increased cytotoxicity in PTEN-deficient sarcoma cell lines in culture (PMID: 26116172). | 26116172 |
| PTEN loss | glioblastoma | sensitive | PKI-402 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PKI-402 inhibited tumor growth in PTEN-negative glioblastoma multiforme cell line xenograft models (PMID: 20371716). | 20371716 |
| PTEN mutant | endometrial cancer | sensitive | Apitolisib | Phase II | Actionable | In a Phase II trial, Apitolisib (GDC-0980) was poorly tolerated, but demonstrated efficacy in endometrial cancer patients harboring mutations in PIK3CA, PTEN, or AKT1 (J Clin Oncol 32:5s, 2014 (suppl; abstr 5513)). | detail... |
| PTEN del | urinary bladder cancer | sensitive | Metformin | Preclinical | Actionable | In a preclinical study, bladder cancer cells with PTEN deletion were sensitive to Glucophage (metformin) in culture, resulting in inhibition of cell growth (PMID: 26921394). | 26921394 |
| PIK3CA wild-type PTEN loss | breast cancer | resistant | AZD8835 | Preclinical | Actionable | In a preclinical study, human breast cancer cells with wild-type PIK3CA and loss of PTEN were resistant to growth inhibition by AZD8835 in culture (PMID: 26839307). | 26839307 |
| PTEN del | prostate cancer | sensitive | AZD8186 + Enzalutamide | Preclinical | Actionable | In a preclinical study, AZD8186 and Xtandi (enzalutamide) combination treatment resulted in suppression of tumor growth in animal models of prostate cancer harboring PTEN gene deletion (PMID: 25544636). | 25544636 |
| PTEN del | prostate cancer | sensitive | Alpelisib + AZD8186 + Enzalutamide | Preclinical | Actionable | In a preclinical study, AZD8186, Alpelisib (BYL719), and Xtandi (enzalutamide) combination treatment resulted in near-complete suppression of tumor growth in animal models of prostate cancer harboring PTEN gene deletion (PMID: 25544636). | 25544636 |
| PTEN del | prostate cancer | sensitive | Alpelisib + AZD8186 | Preclinical | Actionable | In a preclinical study, AZD8186 and Alpelisib (BYL719) combination treatment resulted in minor inhibition of tumor growth in animal models of prostate cancer harboring PTEN gene deletion (PMID: 25544636). | 25544636 |
| PTEN loss | Advanced Solid Tumor | no benefit | SAR260301 | Phase I | Actionable | In a Phase I trial, SAR260301 demonstrated acceptable safety but undesirable pharmacokinetics, and resulted in no response in patients with advanced solid tumors harboring PTEN loss (J Clin Oncol 33, 2015 (suppl; abstr 2564)). | detail... |
| PTEN loss | triple-receptor negative breast cancer | sensitive | AZD6482 + Veliparib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Veliparib (ABT-888) and AZD6482 inhibited growth of triple-negative breast cancer cell lines with PTEN loss in culture (Mol Cancer Res Feb 2016 14; B12). | detail... |
| PTEN loss | triple-receptor negative breast cancer | sensitive | AZD6482 + Rucaparib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Rubraca (rucaparib) and AZD6482 inhibited growth of triple-negative breast cancer cell lines with PTEN loss in culture (Mol Cancer Res Feb 2016 14; B12). | detail... |
| PTEN loss | triple-receptor negative breast cancer | sensitive | AZD6482 + Olaparib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Lynparza (olaparib) and AZD6482 inhibited growth of triple-negative breast cancer cell lines with PTEN loss in culture (Mol Cancer Res Feb 2016 14; B12). | detail... |
| PTEN loss | triple-receptor negative breast cancer | sensitive | AZD6482 + Niraparib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Zejula (niraparib) and AZD6482 inhibited growth of triple-negative breast cancer cell lines with PTEN loss in culture (Mol Cancer Res Feb 2016 14; B12). | detail... |
| PTEN loss | triple-receptor negative breast cancer | sensitive | AZD6482 + Talazoparib | Preclinical | Actionable | In a preclinical study, the combination of Talazoparib (BMN-673) and AZD6482 inhibited growth of triple-negative breast cancer cell lines with PTEN loss in culture (Mol Cancer Res, Feb 2016 14; B12). | detail... |
| PIK3CA mut PTEN loss | breast cancer | sensitive | Alpelisib + AZD6482 | Preclinical - Pdx | Actionable | In a preclinical study, AZD6482 and Alpelisib (BYL719) combination treatment inhibited Akt signaling and growth in a breast cancer patient-derived xenograft (PDX) model harboring a PIK3CA mutation and PTEN loss (Cancer Res October 1, 2014 74; LB-327). | detail... |
| PIK3CA mut PTEN loss | breast cancer | sensitive | Buparlisib | Preclinical - Pdx | Actionable | In a preclinical study, Buparlisib (BKM120) inhibited Akt signaling and growth in a PDX model of breast cancer cells harboring a PIK3CA mutation and PTEN loss ( Cancer Res October 1, 2014 74; LB-327 ). | detail... |
| PIK3CA mut PTEN loss | breast cancer | resistant | Alpelisib | Case Reports/Case Series | Actionable | In a clinical case study, a breast cancer patient harboring a PIK3CA mutation developed resistance to Alpelisib (BYL719) treatment and progressive disease after initial response, accompanied by a loss of PTEN, and the corrresponding patient-derived xenograft model demonstrated resistance to Alpelisib (BYL719)-induced inhibition of tumor growth (PMID: 25409150). | detail... 25409150 |
| PTEN mutant | endometrial cancer | sensitive | A66 + GSK2636771 | Preclinical | Actionable | In a preclinical study, A66 and GSK2636771 combination treatment inhibited viability of endometrioid endometrial cancer cell lines harboring PTEN mutations in culture (PMID: 23674493). | 23674493 |
| PTEN mutant | endometrial cancer | sensitive | A66 + AZD6482 | Preclinical | Actionable | In a preclinical study, A66 and AZD6482 combination treatment inhibited viability of endometrioid endometrial cancer cell lines harboring PTEN mutations in culture (PMID: 23674493). | 23674493 |
| PTEN loss | breast cancer | sensitive | GSK2636771 | Preclinical | Actionable | In a preclinical study, GSK2636771 inhibited viability of breast cancer cell lines harboring PTEN deficiency in culture (PMID: 23674493). | 23674493 |
| PTEN loss | prostate cancer | sensitive | GSK2636771 | Preclinical | Actionable | In a preclinical study, GSK2636771 inhibited viability of prostate cancer cell lines harboring PTEN deficiency in culture (PMID: 23674493). | 23674493 |
| PTEN loss | breast cancer | sensitive | AZD6482 | Preclinical | Actionable | In a preclinical study, AZD6482 inhibited viability of breast cancer cell lines harboring PTEN deficiency in culture (PMID: 23674493). | 23674493 |
| PTEN loss | prostate cancer | sensitive | AZD6482 | Preclinical | Actionable | In a preclinical study, AZD6482 inhibited viability of prostate cancer cell lines harboring PTEN deficiency in culture (PMID: 23674493). | 23674493 |
| PTEN mutant | endometrial cancer | resistant | A66 | Preclinical | Actionable | In a preclinical study, endometrioid endometrial cancer cell lines harboring PTEN mutations demonstrated resistance to A66 induced growth inhibition in culture (PMID: 23674493). | 23674493 |
| PTEN mutant | endometrial cancer | resistant | TGX-221 | Preclinical | Actionable | In a preclinical study, endometrioid endometrial cancer cell lines harboring PTEN mutations demonstrated resistance to TGX-221 induced growth inhibition in culture (PMID: 23674493). | 23674493 |
| PTEN mutant | endometrial cancer | resistant | AZD6482 | Preclinical | Actionable | In a preclinical study, endometrioid endometrial cancer cell lines harboring PTEN mutations demonstrated resistance to AZD6482 induced growth inhibition in culture (PMID: 23674493). | 23674493 |
| PTEN mutant | endometrial cancer | resistant | GSK2636771 | Preclinical | Actionable | In a preclinical study, endometrioid endometrial cancer cell lines harboring PTEN mutations demonstrated resistance to GSK2636771 induced growth inhibition in culture (PMID: 23674493). | 23674493 |
| PTEN mutant | endometrial cancer | no benefit | Temsirolimus | Phase II | Actionable | In a retrospective study of a Phase II trial, mutation status of PTEN was not associated with progression-free survival or response rate in advanced endometrial cancer patients treated with Torisel (temsirolimus) (PMID: 27016228). | 27016228 |
| PTEN dec exp | Advanced Solid Tumor | sensitive | GSK2636771 | Phase Ib/II | Actionable | In a Phase I/II trial, GSK2636771 treatment inhibited Akt signaling, and resulted in partial response in 2% (1/53) and stable disease in 25% (13/53) of patients with PTEN-deficient advanced solid tumors (J Clin Oncol 32:5s, 2014 (suppl; abstr 2514)). | detail... |
| PTEN dec exp | melanoma | sensitive | SAR260301 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, SAR260301 inhibited tumor growth in xenograft models of melanoma cell lines harboring PTEN deficiency (PMID: 24387221). | 24387221 |
| PTEN A126G | prostate cancer | sensitive | AZD6482 | Preclinical | Actionable | In a preclinical study, AZD6482 inhibited Akt signaling and cell migration in prostate cancer cell lines overexpressing PTEN A126G (PMID: 26504226). | 26504226 |
| PTEN A126G | prostate cancer | sensitive | Alpelisib | Preclinical - Cell culture | Actionable | In a preclinical study, Alpelisib (BYL719) inhibited Akt signaling and cell migration in prostate cancer cells expressing PTEN A126G in culture (PMID: 26504226). | 26504226 |
| PTEN loss | uterine corpus sarcoma | sensitive | AT13148 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AT13148 inhibited tumor growth in a PTEN-deficient human uterine sarcoma cell line xenograft model (PMID: 22781553). | 22781553 |
| PTEN loss | prostate cancer | sensitive | AT13148 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AT13148 inhibited tumor growth in a PTEN-deficient human prostate cancer cell line xenograft model (PMID: 22781553). | 22781553 |
| PTEN loss | prostate cancer | sensitive | KU-60019 | Preclinical | Actionable | In a preclinical study, KU-60019 blocked tumor growth in PTEN-deficient human prostate cancer xenograft models (PMID: 25870146). | 25870146 |
| PTEN loss | colon cancer | sensitive | KU-55933 | Preclinical | Actionable | In a preclinical study, KU-55933 induced cell cycle arrest and caspase activation in PTEN deficient human colon cancer cells in culture (PMID: 25870146). | 25870146 |
| PTEN loss | prostate cancer | sensitive | OP449 | Preclinical | Actionable | In a preclinical study, prostate cancer mouse models deficient for Pten demonstrated inhibition of the PI3K/Akt signaling pathway and a decrease in both tumor size and cell proliferation when treated with OP449 (PMID: 26563471). | 26563471 |
| PTEN wild-type | uterine cancer | decreased response | GSK2256098 | Preclinical | Actionable | In a preclinical study, GSK2256098 treatment resulted in a decreased response in uterine cancer cells with PTEN wild-type versus uterine cancer cells harboring a PTEN mutation (PMID: 25833835). | 25833835 |
| PTEN mutant | uterine cancer | sensitive | GSK2256098 | Preclinical | Actionable | In a preclinical study, uterine cancer cells harboring a PTEN mutation demonstrated sensitivity to GSK2256098, resulting in inhibition of Ptk2 (Fak) phosphorylation, decreased tumor growth, and apoptosis both in culture and in mouse models (PMID: 25833835). | 25833835 |
| PTEN del | Advanced Solid Tumor | sensitive | Onatasertib | Phase I | Actionable | In a Phase I trial, CC-223 demonstrated safety and preliminary efficacy in patients with solid tumors, including stable disease for greater than 110 days in 2 patients with PIK3CA mutation or PTEN deletion (PMID: 26177599). | 26177599 |
| BRAF mut PTEN loss | melanoma | no benefit | Pembrolizumab | Preclinical | Actionable | In a preclinical study, Keytruda (pembrolizumab) resulted in no benefit in a melanoma mouse model co-harboring a BRAF mutation and PTEN loss (PMID: 26645196). | 26645196 |
| BRAF mut PTEN loss | melanoma | no benefit | GSK2636771 | Preclinical | Actionable | In a preclinical study, GSK2636771 resulted in no benefit in a melanoma mouse model co-harboring a BRAF mutation and PTEN loss (PMID: 26645196). | 26645196 |
| BRAF mut PTEN loss | melanoma | sensitive | GSK2636771 + Pembrolizumab | Preclinical | Actionable | In a preclinical study, a melanoma mouse model harboring a BRAF mutation and PTEN loss was sensitive to the combination of GSK2636771 and Keytruda (pembrolizumab), demonstrating greater tumor growth inhibition and improved survival when compared to either therapy alone (PMID: 26645196). | 26645196 |
| PTEN loss | melanoma | sensitive | GSK2636771 | Preclinical | Actionable | In a preclinical study, human melanoma cells with PTEN loss were sensitive to GSK2636771, resulting in decreased activation of Akt and some inhibition of tumor growth (PMID: 26645196). | 26645196 |
| PTEN positive | melanoma | sensitive | Nivolumab | Clinical Study - Cohort | Actionable | In a clinical study, melanoma patients with PTEN positive tumors demonstrated a decrease in tumor size when treated with Opdivo (nivolumab) (PMID: 26645196). | 26645196 |
| PTEN positive | melanoma | sensitive | Pembrolizumab | Clinical Study - Cohort | Actionable | In a clinical study, melanoma patients with PTEN positive tumors demonstrated a decrease in tumor size when treated with Keytruda (pembrolizumab) (PMID: 26645196). | 26645196 |
| PTEN dec exp | melanoma | decreased response | Nivolumab | Clinical Study - Cohort | Actionable | In a clinical study, melanoma patients with PTEN expression in less than 10% of tumor cells demonstrated decreased response to anti-PD-1 antibodies, including Opdivo (nivolumab), as compared to patients in which PTEN is present in over 10% of tumor cells (PMID: 26645196). | 26645196 |
| PTEN dec exp | melanoma | decreased response | Pembrolizumab | Clinical Study - Cohort | Actionable | In a clinical study, melanoma patients with PTEN expression in less than 10% of tumor cells demonstrated decreased response to anti-PD-1 antibodies, including Keytruda (pembrolizumab), compared to patients in which PTEN is present in over 10% of tumor cells (PMID: 26645196). | 26645196 |
| PTEN wild-type | melanoma | sensitive | E6201 | Preclinical | Actionable | In a preclinical study, E6201 inhibited proliferation of several melanoma cell lines in culture and sensitivity was associated with wild-type PTEN (PMID: 23039341). | 23039341 |
| PTEN mutant | head and neck squamous cell carcinoma | resistant | Taselisib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, head and neck squamous cell carcinoma cell lines and cell line xenograft models with PTEN alterations were resistant to the apoptotic effects of Taselisib (GDC-0032) (PMID: 26589432). | 26589432 |
| PTEN loss | prostate cancer | no benefit | MK2206 | Phase I | Actionable | In a Phase I clinical trial, 8 patients with metastatic, castration-resistant prostate cancer harboring a loss of PTEN did not respond to MK-2206 therapy, but prolonged stable disease was observed in 2 patients (PMID: 26187616). | 26187616 |
| PTEN loss | prostate cancer | sensitive | Panulisib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Panulisib (P7170) inhibited tumor growth in PTEN null prostate cancer cell xenograft models (PMID: 25700704). | 25700704 |
| PTEN loss | lung squamous cell carcinoma | predicted - sensitive | AZD8186 | Phase I | Actionable | In a Phase I trial, AZD8186 demonstrated preliminary efficacy in patients with tumor types with prevalent PTEN-deficiency, including squamous non-small cell lung cancer (AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT329). | detail... |
| PTEN loss | triple-receptor negative breast cancer | predicted - sensitive | AZD8186 | Phase I | Actionable | In a Phase I trial, AZD8186 demonstrated preliminary efficacy in patients with tumor types with prevalent PTEN-deficiency, including triple negative breast cancer (AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT329). | detail... |
| PTEN del | prostate cancer | predicted - sensitive | AZD8186 | Phase I | Actionable | In a Phase I trial, AZD8186 demonstrated preliminary efficacy in patients with tumor types with prevalent PTEN-deficiency, including prostate cancer (AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT329). | detail... |
| PTEN loss | prostate cancer | sensitive | AZD8186 | Preclinical | Actionable | In a preclinical study, AZD8186 inhibited tumor growth of PTEN deficient prostate xenografts models (PMID: 25514658). | 25514658 |
| PTEN del | Advanced Solid Tumor | no benefit | GSK2636771 | Phase I | Actionable | In a Phase I trial, patients with advanced solid tumors deficient in PTEN lacked benefit from GSK2636771 (PMID: 26117819). | 26117819 |
| PTEN negative | glioblastoma | no benefit | Temozolomide + Vandetanib | Phase II | Actionable | In a Phase II trial, Caprelsa (vandetinib), in combination with radiation therapy and Temodar (temozolomide), demonstrated no difference in PFS and OS when compared between glioblastoma patients negative for PTEN versus those positive for PTEN (PMID: 25910950). | 25910950 |
| PTEN loss VHL loss | renal carcinoma | decreased response | Gedatolisib | Preclinical | Actionable | In a preclinical study, human renal carcinoma cells with PTEN loss and VHL loss had a decreased response to Gedatolisib (PKI-587) in culture (PMID: 21325073). | 21325073 |
| PTEN loss | renal carcinoma | decreased response | Gedatolisib | Preclinical | Actionable | In a preclinical study, human renal carcinoma cells with PTEN loss had a decreased response to Gedatolisib (PKI-587) in culture (PMID: 21325073). | 21325073 |
| PTEN loss | brain glioma | sensitive | Gedatolisib | Preclinical | Actionable | In a preclinical study, Gedatolisib (PKI-587) inhibited growth of human glioma cells with PTEN loss in culture (PMID: 21325073). | 21325073 |
| PTEN del | prostate cancer | sensitive | Gedatolisib | Preclinical | Actionable | In a preclinical study, Gedatolisib (PKI-587) inhibited growth of human prostate cancer cells harboring PTEN deletion in culture (PMID: 21325073, PMID: 14737113). | 14737113 21325073 |
| PTEN A72fs | breast cancer | sensitive | Gedatolisib | Preclinical | Actionable | In a preclinical study, Gedatolisib (PKI-587) inhibited growth of human breast cancer cells harboring PTEN A72fs*5 in culture (PMID: 21325073, PMID: 17314276). | 17314276 21325073 |
| PTEN del | prostate cancer | sensitive | Pictilisib + Vorinostat | Preclinical | Actionable | In a preclinical study, GDC-0941 and Zolinza (vorinostat) acted synergistically to inhibit growth of a human prostate cancer cell line harboring a PTEN deletion in culture (PMID: 9661880, PMID: 22693356). | 22693356 9661880 |
| PTEN del | prostate cancer | sensitive | MEN1611 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, MEN1611 (CH5132799) inhibited tumor growth in xenograft models of a human prostate cancer cell line with deletion of PTEN (PMID: 21558396). | 21558396 |
| PTEN del | stomach cancer | sensitive | MEN1611 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, MEN1611 (CH5132799) induced tumor regression in xenograft models of a human stomach cancer cell line with deletion of PTEN (PMID: 21558396). | 21558396 |
| PIK3CA R38C PTEN loss | endometrial cancer | sensitive | MEN1611 | Preclinical | Actionable | In a preclinical study, MEN1611 (CH5132799) inhibited proliferation of an endometrial cancer cell line harboring PIK3CA R38C and PTEN loss in culture (PMID: 21558396). | 21558396 |
| PTEN del | prostate cancer | sensitive | Rucaparib | Preclinical - Cell culture | Actionable | In a preclinical study, Rubraca (rucaparib) induced senescence and increased radiosensitivity in PTEN null prostate cancer cells in culture (PMID: 23565244). | 23565244 |
| PTEN loss | glioblastoma | sensitive | PF-04691502 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PF-04691502 inhibited Akt phosphorylation, resulted in growth inhibition of PTEN-null glioblastoma cells in culture and in cell line xenograft models (PMID: 21750219). | 21750219 |
| PTEN del | prostate cancer | sensitive | VS-5584 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, VS-5584 inhibited PI3K/mTOR signaling and cell proliferation in a human prostate cancer cell line harboring a PTEN deletion in culture, and inhibited PI3K/MTOR signaling and tumor growth in xenograft models (PMID: 23270925). | 23270925 |
| PIK3CA E365K PTEN mut | endocervical carcinoma | sensitive | Dactolisib | Preclinical | Actionable | In a preclinical study, BEZ235 inhibited proliferation of endometrial cancer cells harboring PIK3CA E365K and PTEN mutations in culture (PMID: 22662154). | 22662154 |
| PTEN mutant | endometrial cancer | sensitive | Everolimus | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Afinitor (everolimus) inhibited growth of endometrial cancer cells harboring a PTEN nonsense mutation in culture and in xenograft models (PMID: 22662154). | 22662154 |
| PTEN mutant | endometrial cancer | sensitive | Dactolisib | Preclinical | Actionable | In a preclinical study, BEZ235 decreased growth of endometrial cancer cells harboring a PTEN nonsense mutation in culture and in xenograft models (PMID: 22662154). | 22662154 |
| PIK3CA E365K PTEN mut | endometrial cancer | sensitive | Dactolisib | Preclinical | Actionable | In a preclinical study, BEZ235 inhibited proliferation of endometrial cancer cells harboring PIK3CA E365K and PTEN mutations in culture (PMID: 22662154). | 22662154 |
| PIK3CA R38C PTEN mut | endometrial cancer | sensitive | Dactolisib | Preclinical | Actionable | In a preclinical study, BEZ235 decreased growth of endometrial cancer cells harboring PIK3CA R38C and PTEN mutations in culture and in xenograft models (PMID: 22662154). | 22662154 |
| PIK3CA R108H PTEN mut | endometrial cancer | sensitive | Dactolisib | Preclinical | Actionable | In a preclinical study, BEZ235 inhibited proliferation of endometrial cancer cells harboring PIK3CA R108H and PTEN mutations in culture (PMID: 22662154). | 22662154 |
| PIK3CA R88Q PTEN mut | endometrial cancer | sensitive | Everolimus | Preclinical | Actionable | In a preclinical study, Afinitor (everolimus) inhibited proliferation of endometrial cancer cells harboring PIK3CA R88Q and PTEN mutations in culture (PMID: 22662154). | 22662154 |
| PIK3CA R88Q PTEN mut | endometrial cancer | sensitive | Dactolisib | Preclinical | Actionable | In a preclinical study, BEZ235 inhibited proliferation of endometrial cancer cells harboring PIK3CA R88Q and PTEN mutations in culture (PMID: 22662154). | 22662154 |
| PTEN mut TP53 mut | skin cancer | sensitive | Sapanisertib | Preclinical | Actionable | In a preclinical study, a skin cancer cell line harboring mutations in PTEN and TP53 demonstrated sensitivity to Sapanisertib (MLN0128) in culture (PMID: 25261369). | 25261369 |
| PTEN mutant | breast cancer | sensitive | Sapanisertib | Preclinical | Actionable | In a preclinical study, Sapanisertib (MLN0128) induced apoptosis and inhibited MTORC1 signaling in breast cancer cells harboring a PTEN mutation (PMID: 25261369). | 25261369 |
| PTEN loss | Advanced Solid Tumor | sensitive | BAY1125976 | Preclinical | Actionable | In a preclinical study, BAY1125976 demonstrated anti-tumor efficacy in multiple xenograft tumor models of different cancers with PIK3CA mutations or PTEN deletions and displayed synergy with other anti-cancer therapies (Cancer Res 2013;73(8 Suppl):Abstract nr 2050). | detail... |
| BRAF V600E PTEN loss | melanoma | predicted - resistant | Everolimus | Case Reports/Case Series | Actionable | In a retrospective analysis, a melanoma patient harboring PTEN loss and BRAF V600E demonstrated resistance to Afinitor (everolimus) treatment, resulting in progressive disease (PMID: 20664172). | 20664172 |
| PTEN negative | Advanced Solid Tumor | conflicting | Talazoparib | Phase II | Actionable | In a Phase II trial, Talzenna (talazoparib) treatment did not result in significant clinical benefit in patients with advanced solid tumors harboring PTEN mutation or loss (by IHC), with one patient harboring a PTEN mutation achieved a prolonged stable disease as best response in a cohort of 13 patients (Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A096; NCT02286687). | detail... |
| PTEN negative | Advanced Solid Tumor | conflicting | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, PTEN-deficient cancer cell lines with DNA repair deficiency demonstrated high sensitivity to the PARP inhibitor Talzenna (talazoparib) (PMID: 23881923). | 23881923 |
| PTEN loss | glioblastoma | sensitive | CCT128930 | Preclinical - Cell line xenograft | Actionable | In preclinical studies, CCT128930 prevented tumor growth in a PTEN-null human glioblastoma cell line xenograft model (PMID: 21191045). | 21191045 |
| PTEN wild-type | glioblastoma | sensitive | 2-Methoxyestradiol | Preclinical | Actionable | In a preclinical study, 2-Methoxyestradiol (2ME2) inhibited tumor-induced angiogenesis and reduced tumor growth in PTEN reconstituted GBM cell lines and mouse models (PMID: 24162827). | 24162827 |
| PTEN loss | lung non-small cell carcinoma | sensitive | Pictilisib | Preclinical - Cell line xenograft | Actionable | In preclinical studies, the PI3K inhibitor GDC-0941 demonstrated efficacy against NSCLC tumor cell lines in both culture and xenograft models harboring alterations in the PI3K pathway (PMID: 23136191). | 23136191 |
| PTEN del | lung non-small cell carcinoma | predicted - sensitive | PF-04691502 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PF-04691502 inhibited tumor growth in PTEN-deleted non-small cell lung cancer cell line xenograft models (PMID: 21750219). | 21750219 |
| PTEN mutant | skin melanoma | not applicable | N/A | Guideline | Risk Factor | Germline PTEN mutations or polymorphisms are associated with increased risk of developing single or multiple primary cutaneous melanomas (NCCN.org). | detail... |
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