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| Profile Name | PTEN loss |
| Gene Variant Detail | |
| Relevant Treatment Approaches | Akt Inhibitor (Pan) Akt1 Inhibitor Akt2 Inhibitor PI3K Inhibitor (Pan) PIK3CB inhibitor |
| Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|---|
| PTEN loss | lung non-small cell carcinoma | sensitive | PI3K Inhibitor (Pan) | 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 | glioblastoma | sensitive | Akt2 Inhibitor | 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 | Advanced Solid Tumor | sensitive | Akt1 Inhibitor Akt2 Inhibitor | 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 | glioblastoma | sensitive | PI3K Inhibitor (Pan) | 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 | brain glioma | sensitive | PI3K Inhibitor (Pan) | 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 | renal carcinoma | decreased response | PI3K Inhibitor (Pan) | 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 | prostate cancer | sensitive | PIK3CB inhibitor | AZD8186 | Preclinical | Actionable | In a preclinical study, AZD8186 inhibited tumor growth of PTEN deficient prostate xenografts models (PMID: 25514658). | 25514658 |
| PTEN loss | triple-receptor negative breast cancer | predicted - sensitive | PIK3CB inhibitor | 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 | lung squamous cell carcinoma | predicted - sensitive | PIK3CB inhibitor | 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 | prostate cancer | sensitive | PI3K Inhibitor (Pan) | 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 | no benefit | Akt Inhibitor (Pan) | 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 | melanoma | sensitive | PIK3CB inhibitor | 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 | 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 | 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 | 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 | 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 | 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 | PIK3CB inhibitor | 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 | sensitive | PIK3CB inhibitor | 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 | PIK3CB inhibitor | 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 | PIK3CB inhibitor | 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 | triple-receptor negative breast cancer | sensitive | PIK3CB inhibitor | 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 | triple-receptor negative breast cancer | sensitive | PIK3CB inhibitor | 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 | PIK3CB inhibitor | 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 | PIK3CB inhibitor | 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 | PIK3CB inhibitor | 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 | Advanced Solid Tumor | no benefit | PIK3CB inhibitor | 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 | PI3K Inhibitor (Pan) | 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 | 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 | 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 | 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 | 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 | 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 | 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 | prostate carcinoma | decreased response | PIK3CB inhibitor | 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 | 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 | 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 | 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 | 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 | 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 | glioblastoma | sensitive | PI3K Inhibitor (Pan) | 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 | 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 | 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 | 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 | sensitive | Akt Inhibitor (Pan) | 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 |
| PTEN loss | renal carcinoma | sensitive | Akt Inhibitor (Pan) | 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 | Advanced Solid Tumor | sensitive | Akt Inhibitor (Pan) | 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 loss | castration-resistant prostate carcinoma | sensitive | Akt Inhibitor (Pan) | 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 | triple-receptor negative breast cancer | sensitive | Akt Inhibitor (Pan) | 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 | 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 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 | 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 | 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 | acute lymphoblastic leukemia | sensitive | PI3K Inhibitor (Pan) | 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 | glioblastoma | sensitive | PI3K Inhibitor (Pan) | 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 | prostate cancer | sensitive | PI3K Inhibitor (Pan) | 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 | breast adenocarcinoma | sensitive | PI3K Inhibitor (Pan) | 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 | prostate cancer | sensitive | PI3K Inhibitor (Pan) | 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 | prostate cancer | sensitive | Akt Inhibitor (Pan) | 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 |
| PTEN loss | head and neck squamous cell carcinoma | predicted - sensitive | PI3K Inhibitor (Pan) | 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 | colorectal cancer | sensitive | PIK3CB inhibitor | 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 | head and neck squamous cell carcinoma | predicted - sensitive | PI3K Inhibitor (Pan) | 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 | head and neck squamous cell carcinoma | predicted - sensitive | PI3K Inhibitor (Pan) | 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 | breast adenocarcinoma | sensitive | Akt Inhibitor (Pan) | 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 | diffuse large B-cell lymphoma | predicted - sensitive | Akt Inhibitor (Pan) | 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 | 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 | 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 | 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 | lung squamous cell carcinoma | no benefit | PI3K Inhibitor (Pan) | 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 | breast cancer | no benefit | Akt Inhibitor (Pan) | 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 | 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 | osteosarcoma | sensitive | Akt Inhibitor (Pan) | 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 | 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 | 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 | 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 | 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 | sensitive | Akt Inhibitor (Pan) | 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 | sensitive | Akt Inhibitor (Pan) | 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 | Akt Inhibitor (Pan) | 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 | Akt Inhibitor (Pan) | 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 | Akt Inhibitor (Pan) | 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 | lung squamous cell carcinoma | no benefit | Akt Inhibitor (Pan) | 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 |
| PTEN loss | stomach cancer | sensitive | Akt Inhibitor (Pan) | 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 | stomach cancer | sensitive | Akt Inhibitor (Pan) | 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 | triple-receptor negative breast cancer | predicted - sensitive | Akt Inhibitor (Pan) | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 + 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 | castration-resistant prostate carcinoma | sensitive | Akt Inhibitor (Pan) | 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 | 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 loss | castration-resistant prostate carcinoma | no benefit | PIK3CB inhibitor | 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 loss | glioblastoma | predicted - sensitive | Akt Inhibitor (Pan) | 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... |
| PTEN loss | stomach cancer | no benefit | PIK3CB inhibitor | 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 (2.8 vs 4.0 months) or median overall survival (7.0 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 (PMID: 37883723; NCT02951091). | 37883723 |
| 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 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 | 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 loss | Advanced Solid Tumor | no benefit | Talazoparib | Phase II | Actionable | In a Phase II trial, Talzenna (talazoparib) treatment resulted in limited clinical benefit in patients with advanced solid tumors harboring PTEN deleterious mutations or loss (by IHC), with a clinical benefit rate of 9.4% (1/14, 1 with stable disease >/=24 weeks) and a median overall survival of 8.5 months and a median progression-free survival of 7.7 weeks (PMID: 39085400; NCT02286687). | 39085400 | |
| PTEN loss | meningioma | predicted - sensitive | Bevacizumab + Everolimus | Case Reports/Case Series | Actionable | In a clinical case study, treatment with the combination of Afinitor (everolimus) and Avastin (bevacizumab) resulted in a partial response with a progression-free survival of 382 days in a meningioma patient with PTEN loss (by IHC) (PMID: 39143272). | 39143272 | |
| PTEN loss | prostate cancer | sensitive | Akt Inhibitor (Pan) | Ipatasertib + Onvansertib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, treatment with the combination of Ipatasertib (GDC-0068) and Onvansertib (PCM-075) resulted in greater tumor growth inhibition compared to either therapy alone in PTEN-deficient prostate cancer cell line xenograft models (PMID: 38894678). | 38894678 |