Molecular Profile Detail

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Profile Name PTEN del
Gene Variant Detail

PTEN del (loss of function)

Relevant Treatment Approaches Akt Inhibitor (Pan) Akt1 Inhibitor Akt2 Inhibitor PI3K Inhibitor (Pan) PIK3CB inhibitor

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
PTEN del lung non-small cell carcinoma predicted - sensitive PI3K Inhibitor (Pan) 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 del prostate cancer sensitive PI3K Inhibitor (Pan) 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
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 del stomach cancer sensitive PI3K Inhibitor (Pan) 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
PTEN del prostate cancer sensitive PI3K Inhibitor (Pan) 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 prostate cancer sensitive PI3K Inhibitor (Pan) 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 PI3K Inhibitor (Pan) 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 del Advanced Solid Tumor no benefit PIK3CB inhibitor 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 del prostate 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 prostate cancer (AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT329). detail...
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
PTEN del prostate cancer sensitive PIK3CB inhibitor 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 del prostate cancer sensitive PIK3CB inhibitor 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 PIK3CB inhibitor 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 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
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 del prostate cancer sensitive Akt Inhibitor (Pan) 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 del breast cancer sensitive PI3K Inhibitor (Pan) 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 del glioblastoma no benefit PI3K Inhibitor (Pan) 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 prostate cancer not predictive PI3K Inhibitor (Pan) 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 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 del endometrial carcinoma sensitive PI3K Inhibitor (Pan) 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 sensitive PI3K Inhibitor (Pan) 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 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 del Advanced Solid Tumor no benefit Akt Inhibitor (Pan) 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...