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Profile Name | PTEN del |
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 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | stomach cancer | sensitive | PI3K Inhibitor (Pan) | CH5132799 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, 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) | 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 | 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 | 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 | 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 | 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 | 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) | CH5132799 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, CH5132799 inhibited tumor growth in xenograft models of a human prostate cancer cell line with deletion of PTEN (PMID: 21558396). | 21558396 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
---|---|---|---|---|---|---|
NCT02465060 | Phase II | Erdafitinib Trametinib Crizotinib Sapanisertib AZD4547 Dasatinib Osimertinib Palbociclib Capivasertib Larotrectinib Ulixertinib Nivolumab + Relatlimab Copanlisib Sunitinib Nivolumab Pertuzumab + Trastuzumab Ipatasertib Dabrafenib + Trametinib Binimetinib Adavosertib Afatinib Defactinib GSK2636771 Vismodegib Ado-trastuzumab emtansine Taselisib | Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial) | Recruiting | USA | 2 |
NCT05082025 | Phase II | Copanlisib + Fulvestrant | Phase 2 Study of PI3K Inhibitor Copanlisib in Combination With Fulvestrant in Selected ER+ and/or PR+ Cancers With PI3K (PIK3CA, PIK3R1) and/or PTEN Alterations | Not yet recruiting | USA | 0 |
NCT05038839 | Phase I | Cabozantinib + Pamiparib | Cabozantinib and Pamiparib for the Treatment of Advanced of Refractory Solid Tumors | Recruiting | USA | 0 |
NCT01884285 | Phase I | AZD8186 Abiraterone + AZD8186 AZD8186 + Vistusertib | AZD8186 First Time In Patient Ascending Dose Study | Completed | USA | ESP | CAN | 1 |