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Gene | PTEN |
Variant | dec exp |
Impact List | none |
Protein Effect | no effect |
Gene Variant Descriptions | PTEN dec exp indicates decreased expression of the Pten protein and/or mRNA. However, the mechanism causing the decreased expression is unspecified. |
Associated Drug Resistance | |
Category Variants Paths |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
PTEN dec exp | renal cell carcinoma | no benefit | Everolimus | Case Reports/Case Series | Actionable | In a retrospective analysis from a Phase II clinical trial, patients with metastatic renal cell carcinoma treated with Afinitor (everolimus) had no difference in progression-free survival when stratified by high expression (n=17) and low expression (n=21) of Pten (PMID: 26951309). | 26951309 |
PTEN dec exp | triple-receptor negative breast cancer | sensitive | Ipatasertib | Preclinical - Pdx | Actionable | In a preclinical study, Ipatasertib (GDC-0068) reduced tumor growth in a patient-derived xenograft (PDX) model of triple-negative breast cancer with low PTEN expression (PMID: 32205017). | 32205017 |
PTEN dec exp | renal cell carcinoma | no benefit | Apitolisib | Case Reports/Case Series | Actionable | In a retrospective analysis from a Phase II clinical trial, patients with metastatic renal cell carcinoma treated with Apitolisib (GDC-0980) had no difference in progression-free survival when stratified by high expression (n=17) and low expression (n=19) of Pten (PMID: 26951309). | 26951309 |
PTEN dec exp | Advanced Solid Tumor | sensitive | GSK2636771 | Phase Ib/II | Actionable | In a Phase I/II trial, GSK2636771 treatment inhibited Akt signaling, and resulted in partial response in 2% (1/53) and stable disease in 25% (13/53) of patients with PTEN-deficient advanced solid tumors (J Clin Oncol 32:5s, 2014 (suppl; abstr 2514)). | detail... |
PTEN dec exp | melanoma | sensitive | SAR260301 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, SAR260301 inhibited tumor growth in xenograft models of melanoma cell lines harboring PTEN deficiency (PMID: 24387221). | 24387221 |
PTEN dec exp | melanoma | decreased response | Nivolumab | Clinical Study - Cohort | Actionable | In a clinical study, melanoma patients with PTEN expression in less than 10% of tumor cells demonstrated decreased response to anti-PD-1 antibodies, including Opdivo (nivolumab), as compared to patients in which PTEN is present in over 10% of tumor cells (PMID: 26645196). | 26645196 |
PTEN dec exp | triple-receptor negative breast cancer | predicted - sensitive | Alpelisib + Everolimus | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, combination treatment with Piqray (albelisib) and Afinitor (everolimus) synergistically inhibited cell viability of PTEN-deficient triple-negative breast cancer patient-derived cells in culture, and led to inhibition of tumor growth in patient-derived xenograft (PDX) models (PMID: 36900375). | 36900375 |
PTEN dec exp | melanoma | decreased response | Pembrolizumab | Clinical Study - Cohort | Actionable | In a clinical study, melanoma patients with PTEN expression in less than 10% of tumor cells demonstrated decreased response to anti-PD-1 antibodies, including Keytruda (pembrolizumab), compared to patients in which PTEN is present in over 10% of tumor cells (PMID: 26645196). | 26645196 |
PTEN dec exp | Advanced Solid Tumor | predicted - sensitive | Pemetrexed Disodium + Sorafenib | Phase I | Actionable | In a Phase I clinical trial, low Pten expression or lack of Pten expression was associated with better response to treatment with the combination of Alimta (pemetrexed) and Nexavar (sorafenib) in patients with advanced solid tumors (PMID: 27213589). | 27213589 |
PTEN dec exp | triple-receptor negative breast cancer | predicted - sensitive | Ipatasertib + Paclitaxel | Phase II | Actionable | In a Phase II trial, Ipatasertib (GDC-0068) in combination with Abraxane (paclitaxel) resulted in improved progression free survival (6.2 vs 3.7 months) compared to placebo in triple-receptor negative breast cancer patients with low Pten expression (PMID: 28800861; NCT02162719). | 28800861 |
PTEN dec exp | triple-receptor negative breast cancer | sensitive | Docetaxel + Ipatasertib | Preclinical - Pdx | Actionable | In a preclinical study, the combination of Ipatasertib (GDC-0068) and Taxotere (docetaxel) inhibited tumor growth in a patient-derived xenograft (PDX) model of triple-negative breast cancer with low PTEN expression, and demonstrated increased activity over either agent alone (PMID: 32205017). | 32205017 |
PTEN dec exp | stomach cancer | no benefit | Fluorouracil + Ipatasertib + Leucovorin + Oxaliplatin | Phase II | Actionable | In a Phase II trial, the combination of Ipatasertib (GDC-0068) and mFOLFOX6 did not improve median progression-free survival (7.1 vs 7.4 months; HR=1.07, p=0.86) compared to placebo plus mFOLFOX6 in patients with advanced gastric or gastroesophageal junction cancer harboring decreased PTEN expression (IHC=0 in >10% of tumor cells) (PMID: 30592991; NCT01896531). | 30592991 |
PTEN dec exp | gastroesophageal cancer | no benefit | Fluorouracil + Ipatasertib + Leucovorin + Oxaliplatin | Phase II | Actionable | In a Phase II trial, the combination of Ipatasertib (GDC-0068) and mFOLFOX6 did not improve median progression-free survival (7.1 vs 7.4 months; HR=1.07, p=0.86) compared to placebo plus mFOLFOX6 in patients with advanced gastroesophageal junction or gastric cancer harboring decreased PTEN expression (IHC=0 in >10% of tumor cells) (PMID: 30592991; NCT01896531). | 30592991 |