Gene Variant Detail

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Gene PTEN
Variant loss
Impact List unknown
Protein Effect loss of function
Gene Variant Descriptions PTEN loss indicates a loss of the PTEN gene, mRNA, and protein, which leads to suppression of Ar-dependent gene expression (PMID: 21620777), epithelial-mesenchymal transition in cell culture (PMID: 20032390), and promotes KRAS-dependent tumor formation (PMID: 20807812), and decreased apoptosis and increased cell survival in a mouse model (PMID: 12782594). PTEN loss has been identified in a number of cancers (PMID: 30738865), including prostate cancer (PMID: 29460925) and glioblastoma (PMID: 9331071).
Associated Drug Resistance

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No Variant Reference Transcript is Available.
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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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 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 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 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
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 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 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 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 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 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 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
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 loss transitional cell carcinoma resistant Everolimus Phase II 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 compared to 0% of patients with controlled disease demonstrating no evidence of PTEN loss (PMID: 22473592). 22473592
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...
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 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 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 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 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 + 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 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
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 loss triple-receptor negative breast cancer predicted - sensitive Capivasertib + Paclitaxel Phase II Actionable In a Phase II trial (PAKT), addition of Capivasertib (AZD5363) 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 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 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 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 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 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...
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 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 Advanced Solid Tumor sensitive Capivasertib Preclinical - Cell culture Actionable In a preclinical study, AZD5363 inhibited growth of various solid tumor cell culture models with loss of Pten (PMID: 22294718). 22294718
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 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 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
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 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 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 prostate cancer sensitive Ipatasertib Phase I 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
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 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
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 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...
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 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 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 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 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 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 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 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 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...
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 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 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 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 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 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 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
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 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
PTEN loss lung squamous cell carcinoma no benefit Capivasertib Case Reports/Case Series Actionable In a Phase II trial (NLMT), Capivasertib (AZD5363) treatment did not result in a conformed 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
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 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 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 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 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 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 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 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 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 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 loss prostate cancer sensitive Capivasertib Preclinical Actionable In a preclinical study, treatment with AZD5363 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
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 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 prostate cancer sensitive AZD8186 Preclinical Actionable In a preclinical study, AZD8186 inhibited tumor growth of PTEN deficient prostate xenografts models (PMID: 25514658). 25514658
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 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 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 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 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 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 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 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 loss breast cancer sensitive Fulvestrant + MK2206 + Ribociclib Preclinical - Cell culture Actionable In a preclinical study, the combination of Ibrance (palbociclib), Faslodex (fulvestrant), and MK2206 inhibited growth of PTEN-deficient breast cancer cells in culture (PMID: 31594766). 31594766
PTEN loss renal carcinoma sensitive Capivasertib Preclinical - Pdx Actionable In a preclinical study, AZD5363 inhibited growth of renal cancer Pdx models with Pten loss (PMID: 22294718). 22294718
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 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
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 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 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 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
PIK3CA R38C PTEN loss endometrial cancer sensitive CH5132799 Preclinical Actionable In a preclinical study, CH5132799 inhibited proliferation of an endometrial cancer cell line harboring PIK3CA R38C and PTEN loss in culture (PMID: 21558396). 21558396
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
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 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
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
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 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 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
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
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 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 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
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 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
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 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 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 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
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 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
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
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
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
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 BFAF V600E and PTEN loss in cell culture (PMID: 19276360). 19276360
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
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
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 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
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
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 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 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
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
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 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 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 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 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
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
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
PTEN loss TP53 loss prostate cancer sensitive Capivasertib Preclinical Actionable In a preclinical study, treatment with AZD5363 improved overall survival and progression-free survival in mouse models of prostate cancer with inactivated PTEN and TP53 (PMID: 26910118). 26910118
PIK3CA E545K 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
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 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
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
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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
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 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 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 inact mut triple-receptor negative breast cancer predicted - sensitive Capivasertib + Paclitaxel Phase II Actionable In a Phase II trial (PAKT), addition of Capivasertib (AZD5363) 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 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 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 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 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 Advanced Solid Tumor sensitive Capivasertib Preclinical - Cell culture Actionable In a preclinical study, AZD5363 inhibited growth of various solid tumor cell culture models with inactivating Pten mutations (PMID: 22294718). 22294718
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 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 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...
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 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 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 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 sensitive GDC-0980 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 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
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 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 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 lung adenocarcinoma no benefit Capivasertib Case Reports/Case Series Actionable In a Phase II trial (NLMT), Capivasertib (AZD5363) treatment did not result in a conformed 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 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 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 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 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 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
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 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 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 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 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 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...