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| Gene | PTEN |
| Variant | del |
| Impact List | deletion |
| Protein Effect | loss of function |
| Gene Variant Descriptions | PTEN del indicates a deletion of the PTEN gene. |
| Associated Drug Resistance | |
| Category Variants Paths |
PTEN mutant PTEN inact mut PTEN del |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| PTEN del | lung non-small cell carcinoma | predicted - sensitive | PF-04691502 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PF-04691502 inhibited tumor growth in PTEN-deleted non-small cell lung cancer cell line xenograft models (PMID: 21750219). | 21750219 |
| PTEN del | prostate cancer | sensitive | VS-5584 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, VS-5584 inhibited PI3K/mTOR signaling and cell proliferation in a human prostate cancer cell line harboring a PTEN deletion in culture, and inhibited PI3K/MTOR signaling and tumor growth in xenograft models (PMID: 23270925). | 23270925 |
| 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 | 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 | 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 | 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 | 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 | GSK2636771 | Case Reports/Case Series | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | Atezolizumab + Ipatasertib | Phase II | Actionable | In a Phase II trial (CRAFT), treatment with Ipatasertib (GDC-0068) plus Tecentriq (atezolizumab) demonstrated safety but limited clinical benefit in advanced solid tumor patients harboring PI3K-AKT pathway mutations (n=13), including PTEN deletion/inactivating mutations or activating mutations in PIK3CA or AKT1, with a partial response in a breast cancer patient with AKT1 E17K and stable disease in a prostate cancer patient with PTEN loss (Ann Oncol (2023) 34 (suppl_2): S256-S257;NCT04551521). | detail... |
| PTEN del | breast cancer | sensitive | MEN1611 | Preclinical - Cell culture | Actionable | In a preclinical study, MEN1611 (CH5132799) inhibited viability in breast cancer cell lines harboring a PTEN deletion in culture (PMID: 36913051). | 36913051 |
| PTEN del | breast carcinoma | sensitive | Quercetin | Preclinical - Cell culture | Actionable | In a preclinical study, Quercetin treatment decreased Akt phosphorylation and inhibited proliferation in a breast cancer cell line harboring homozygous deletion of PTEN in culture (PMID: 16619521). | 16619521 |
| PTEN del | colon cancer | sensitive | Aspirin | Guideline | Actionable | Aspirin is included in guidelines as adjuvant therapy (category 2A) for patients with advanced colon cancer harboring deep PTEN deletions and other somatic mutations affecting the PI3K pathway genes PIK3CA, PIK3R1, or PTEN (NCCN.org). | detail... |
| PTEN del | rectum cancer | sensitive | Aspirin | Guideline | Actionable | Aspirin is included in guidelines as adjuvant therapy (category 2A) for patients with advanced rectal cancer harboring deep PTEN deletions and other somatic mutations affecting the PI3K pathway genes PIK3CA, PIK3R1, or PTEN (NCCN.org). | detail... |