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| Gene | PTEN |
| Variant | loss |
| Impact List | unknown |
| Protein Effect | loss of function |
| Gene Variant Descriptions | PTEN loss indicates a loss of the PTEN gene, mRNA, and protein, which leads to suppression of Ar-dependent gene expression (PMID: 21620777), epithelial-mesenchymal transition in cell culture (PMID: 20032390), and promotes KRAS-dependent tumor formation (PMID: 20807812), and decreased apoptosis and increased cell survival in a mouse model (PMID: 12782594). PTEN loss has been identified in a number of cancers (PMID: 30738865), including prostate cancer (PMID: 29460925) and glioblastoma (PMID: 9331071). |
| Associated Drug Resistance | |
| Category Variants Paths |
PTEN mutant PTEN inact mut PTEN loss |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| PIK3CA R38C PTEN loss | endometrial cancer | sensitive | CH5132799 | Preclinical | Actionable | In a preclinical study, CH5132799 inhibited proliferation of an endometrial cancer cell line harboring PIK3CA R38C and PTEN loss in culture (PMID: 21558396). | 21558396 |
| PTEN loss VHL loss | renal carcinoma | decreased response | Gedatolisib | Preclinical | Actionable | In a preclinical study, human renal carcinoma cells with PTEN loss and VHL loss had a decreased response to Gedatolisib (PKI-587) in culture (PMID: 21325073). | 21325073 |
| BRAF mut PTEN loss | melanoma | sensitive | GSK2636771 + Pembrolizumab | Preclinical | Actionable | In a preclinical study, a melanoma mouse model harboring a BRAF mutation and PTEN loss was sensitive to the combination of GSK2636771 and Keytruda (pembrolizumab), demonstrating greater tumor growth inhibition and improved survival when compared to either therapy alone (PMID: 26645196). | 26645196 |
| BRAF mut PTEN loss | melanoma | no benefit | GSK2636771 | Preclinical | Actionable | In a preclinical study, GSK2636771 resulted in no benefit in a melanoma mouse model co-harboring a BRAF mutation and PTEN loss (PMID: 26645196). | 26645196 |
| BRAF mut PTEN loss | melanoma | no benefit | Pembrolizumab | Preclinical | Actionable | In a preclinical study, Keytruda (pembrolizumab) resulted in no benefit in a melanoma mouse model co-harboring a BRAF mutation and PTEN loss (PMID: 26645196). | 26645196 |
| BRAF mut PTEN loss | melanoma | sensitive | SAR260301 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, SAR260301 inhibited proliferation of PTEN deficient melanoma cells harboring BRAF mutations in culture and suppressed tumor growth in cell line xenograft models (PMID: 27196754). | 27196754 |
| BRAF mut PTEN loss | melanoma | sensitive | SAR260301 + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, SAR260301 and Zelboraf (vemurafenib) synergistically inhibited proliferation of PTEN deficient melanoma cells harboring BRAF mutations in culture and suppressed tumor growth in cell line xenograft models (PMID: 27196754). | 27196754 |
| BRAF mut PTEN loss | melanoma | sensitive | SAR260301 + Selumetinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, SAR260301 and Selumetinib (AZD6244) synergistically inhibited proliferation of PTEN deficient melanoma cells harboring BRAF mutations in culture and suppressed tumor growth in cell line xenograft models (PMID: 27196754). | 27196754 |
| PTEN loss STK11 loss | endometrial cancer | sensitive | Pictilisib | Preclinical | Actionable | In a preclinical study, the PI3K inhibitor GDC-0941 reduced tumor growth rate in immunodeficient mice engrafted with endometrial tumors from PTEN/STK11 (LKB1) deficient mice (PMID: 24322983). | 24322983 |
| PIK3CA mut PTEN loss | breast cancer | resistant | Alpelisib | Case Reports/Case Series | Actionable | In a clinical case study, a breast cancer patient harboring a PIK3CA mutation developed resistance to Alpelisib (BYL719) treatment and progressive disease after initial response, accompanied by a loss of PTEN, and the corrresponding patient-derived xenograft model demonstrated resistance to Alpelisib (BYL719)-induced inhibition of tumor growth (PMID: 25409150). | detail... 25409150 |
| PIK3CA mut PTEN loss | breast cancer | sensitive | Buparlisib | Preclinical - Pdx | Actionable | In a preclinical study, Buparlisib (BKM120) inhibited Akt signaling and growth in a PDX model of breast cancer cells harboring a PIK3CA mutation and PTEN loss ( Cancer Res October 1, 2014 74; LB-327 ). | detail... |
| PIK3CA mut PTEN loss | breast cancer | sensitive | Alpelisib + AZD6482 | Preclinical - Pdx | Actionable | In a preclinical study, AZD6482 and Alpelisib (BYL719) combination treatment inhibited Akt signaling and growth in a breast cancer patient-derived xenograft (PDX) model harboring a PIK3CA mutation and PTEN loss (Cancer Res October 1, 2014 74; LB-327). | detail... |
| PIK3CA mut PTEN loss | prostate cancer | sensitive | PKI-179 | Preclinical - Cell culture | Actionable | In a preclinical study, PKI-179 inhibited growth of prostate cancer cells harboring PIK3CA mutations and PTEN loss in culture (PMID: 20797855). | 20797855 |
| PIK3CA wild-type PTEN loss | breast cancer | resistant | AZD8835 | Preclinical | Actionable | In a preclinical study, human breast cancer cells with wild-type PIK3CA and loss of PTEN were resistant to growth inhibition by AZD8835 in culture (PMID: 26839307). | 26839307 |
| PIK3CA wild-type PTEN loss | breast cancer | no benefit | Everolimus + U0126 | Preclinical - Cell culture | Actionable | In a preclinical study, breast cancer cells harboring PIK3CA wild-type and PTEN loss did not demonstrate any benefit when treated with a combination of Afinitor (everolimus) and U0126 (PMID: 21358673). | 21358673 |
| PIK3CA wild-type PTEN loss | breast cancer | no benefit | Everolimus + Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, breast cancer cells harboring PIK3CA wild-type and PTEN loss did not demonstrate any benefit when treated with a combination of Afinitor (everolimus) and Selumetinib (AZD6244) (PMID: 21358673). | 21358673 |
| PIK3CA wild-type PTEN loss | breast cancer | sensitive | Torkinib + U0126 | Preclinical - Cell culture | Actionable | In a preclinical study, breast cancer cells harboring PIK3CA wild-type and PTEN loss demonstrated sensitivity to the combination treatment of Torkinib (PP242) and U0126 in culture (PMID: 21358673). | 21358673 |
| PIK3CA wild-type PTEN loss | breast cancer | sensitive | Selumetinib + Torkinib | Preclinical - Cell culture | Actionable | In a preclinical study, breast cancer cells harboring PIK3CA wild-type and PTEN loss demonstrated sensitivity to the combination treatment of Torkinib (PP242) and Selumetinib (AZD6244) in culture (PMID: 21358673). | 21358673 |
| PTEN loss RB1 loss | triple-receptor negative breast cancer | no benefit | Palbociclib + Pictilisib | Preclinical | Actionable | In a preclinical study, the combination of Ibrance (palbociclib) and Pictilisib (GDC-0941) did not improve growth inhibition compared to single drug treatment in triple-receptor negative breast cancer cell lines harboring PTEN and RB1 loss in culture (PMID: 27020857). | 27020857 |
| PTEN loss RB1 loss | triple-receptor negative breast cancer | resistant | Pictilisib | Preclinical | Actionable | In a preclinical study, a triple-receptor negative breast cancer line harboring PTEN and RB1 loss was resistant to Pictilisib (GDC-0941) induced growth inhibition in culture (PMID: 27020857). | 27020857 |
| PTEN loss RB1 loss | triple-receptor negative breast cancer | resistant | Palbociclib | Preclinical | Actionable | In a preclinical study, a triple-receptor negative breast cancer line harboring PTEN and RB1 loss was resistant to Ibrance (palbociclib) induced growth inhibition in culture (PMID: 27020857). | 27020857 |
| BRAF V600E PTEN loss | melanoma | predicted - resistant | Everolimus | Case Reports/Case Series | Actionable | In a retrospective analysis, a melanoma patient harboring PTEN loss and BRAF V600E demonstrated resistance to Afinitor (everolimus) treatment, resulting in progressive disease (PMID: 20664172). | 20664172 |
| BRAF V600E PTEN loss | melanoma | sensitive | XL147 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, XL147 inhibited tumor growth in xenograft models of a PTEN-deficient human melanoma cell line harboring BRAF V600E (PMID: 25637314). | 25637314 |
| BRAF V600E PTEN loss | melanoma | sensitive | Pictilisib + PLX4720 | Preclinical | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and PTEN loss demonstrated sensitivity when treated with a combination of Pictilisib (GDC-0941) and PLX4720, resulting in decreased cell proliferation in culture (PMID: 24265153). | 24265153 |
| BRAF V600E PTEN loss | melanoma | sensitive | GDC0879 + Pictilisib | Preclinical - Cell culture | Actionable | In a preclinical study, GDC0879 and Pictilisib (GDC-0941) synergistically inhibited survival of melanoma cell lines harboring BRAF V600E and PTEN loss in cell culture (PMID: 19276360). | 19276360 |
| BRAF V600E PTEN loss | melanoma | sensitive | GSK2636771 + unspecified PD-1 antibody | Preclinical | Actionable | In a preclinical study, treatment with the combination of GSK2636771 and a PD-1 antibody resulted in greater tumor infiltration of T-cells and tumor growth inhibition in mouse melanoma models expressing BRAF V600E with PTEN loss compared to either agent alone (PMID: 26645196). | 26645196 |
| BRAF V600E PTEN loss | melanoma | sensitive | unspecified PD-1 antibody + VE800 | Preclinical | Actionable | In a preclinical study, PD-1 antibody treatment supplemented with VE800 inhibited tumor growth in a transgenic mouse model of melanoma harboring PTEN loss and BRAF V600E (PMID: 30675064). | 30675064 |
| BRAF V600E PTEN loss | melanoma | predicted - sensitive | Dabrafenib + Enzalutamide + Trametinib | Preclinical | Actionable | In a preclinical study, addition of Xtandi (enzalutamide) to Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy improved tumor control and led to a greater reduction in tumor volume in an allograft mouse model of melanoma harboring BRAF V600E and PTEN loss (PMID: 35705814). | 35705814 |
| BRAF V600D PTEN loss | melanoma | sensitive | XL147 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, XL147 inhibited tumor growth in xenograft models of a PTEN-deficient human melanoma cell line harboring BRAF V600D (PMID: 25637314). | 25637314 |
| BRAF V600E PTEN loss TP53 wild-type | colorectal cancer | sensitive | PD-0325901 + Sapanisertib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 synergistically inhibited Erk and PI3K signaling and proliferation, induced apoptosis in TP53-wild-type colorectal cancer cells harboring BRAF V600E and PTEN loss in culture and in cell line xenograft models (PMID: 26272063). | 26272063 |
| PIK3CA R88L PIK3CA E453del PIK3CA T1052K PTEN loss PTEN mut | endometrial carcinoma | sensitive | Copanlisib | Phase I | Actionable | In a Phase I clinical trial, an endometrial carcinoma patient harboring PIK3CA T1052K, R88L, and E453del, as well as a PTEN mutation and loss of PTEN protein expression demonstrated a complete response to treatment with Aliqopa (copanlisib) (PMID: 27672108). | 27672108 |
| PIK3CA H1047R PTEN loss | breast cancer | no benefit | Dactolisib + Venetoclax | Preclinical - Cell culture | Actionable | In a preclinical study, inhibition of Pi3k signaling by BEZ235 did not sensitize breast cancer cell lines harboring PIK3CA H1047R and PTEN loss to Venclexta (venetoclax) in culture (PMID: 27974663). | 27974663 |
| PIK3CA H1047R PTEN loss | breast cancer | predicted - sensitive | Dactolisib + WEHI-539 | Preclinical - Cell culture | Actionable | In a preclinical study, inhibition of Pi3k signaling by BEZ235 sensitized breast cancer cell lines harboring PIK3CA H1047R and PTEN loss to WEHI-539 in culture (PMID: 27974663). | 27974663 |
| PIK3CA H1047R PTEN loss | triple-receptor negative breast cancer | predicted - sensitive | ABT-737 + Dactolisib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, ABT-737 and BEZ235 combination treatment resulted in tumor regression in cell line xenograft models of triple-receptor negative breast cancer harboring PIK3CA H1047R and PTEN loss (PMID: 27974663). | 27974663 |
| PIK3CA H1047R PTEN loss | triple-receptor negative breast cancer | predicted - sensitive | ABT-737 + Sapanisertib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, ABT-737 and Sapanisertib (MLN0128) combination treatment resulted in inhibition of tumor growth in cell line xenograft models of triple-receptor negative breast cancer harboring PIK3CA H1047R and PTEN loss (PMID: 27974663). | 27974663 |
| PIK3CA H1047R PTEN loss | breast cancer | predicted - sensitive | CYH33 | Preclinical - Cell culture | Actionable | In a preclinical study, CYH33 inhibited proliferation of a breast cancer cell line harboring PIK3CA H1047R and PTEN loss in culture (PMID: 30003928). | 30003928 |
| PIK3CA H1047R PTEN loss | breast cancer | sensitive | Taselisib | Preclinical - Cell culture | Actionable | In a preclinical study, a breast cancer cell line harboring a PIK3CA H1047R and PTEN loss was sensitive to treatment with Taselisib (GDC-0032) in culture, demonstrating decreased cell viability (PMID: 31534012). | 31534012 |
| PIK3CA E542K PTEN loss | breast cancer | predicted - sensitive | Dactolisib + WEHI-539 | Preclinical - Cell culture | Actionable | In a preclinical study, inhibition of Pi3k signaling by BEZ235 sensitized breast cancer cell lines harboring PIK3CA E542K and PTEN loss to WEHI-539 in culture (PMID: 27974663). | 27974663 |
| PIK3CA E542K PTEN loss | stomach cancer | unknown | Sirolimus | Phase 0 | Actionable | In a pilot clinical trial, Rapamune (sirolimus) demonstrated modest clinical activity in patients with PIK3CA-mutant gastric cancer (n=3) or hilar cholangiocarcinoma (n=1), including a gastric cancer patient harboring PIK3CA E542K and PTEN loss, with a 0% response rate, median progression-free survival of 1.9 months, and median overall survival of 3.6 months (PMID: 28685070). | 28685070 |
| PIK3CA E542K PTEN loss | lung squamous cell carcinoma | sensitive | Alpelisib | Preclinical - Pdx | Actionable | In a preclinical study, Alpelisib (BYL719) treatment resulted in response in a lung squamous cell carcinoma patient-derived xenograft (PDX) model harboring PIK3CA E542K and PTEN loss (PMID: 30093452). | 30093452 |
| PIK3CA E542K PTEN loss | breast cancer | predicted - sensitive | CYH33 | Preclinical - Cell culture | Actionable | In a preclinical study, CYH33 inhibited proliferation of a breast cancer cell line harboring PIK3CA E542K and PTEN loss in culture (PMID: 30003928). | 30003928 |
| PIK3CA E542K PTEN loss | breast cancer | sensitive | Taselisib | Preclinical - Cell culture | Actionable | In a preclinical study, a breast cancer cell line harboring PIK3CA E542K was sensitive to treatment with Taselisib (GDC-0032) in culture, demonstrating decreased cell viability (PMID: 31534012). | 31534012 |
| PIK3CA E542K PTEN loss | lung squamous cell carcinoma | sensitive | Buparlisib | Preclinical - Pdx | Actionable | In a preclinical study, Buparlisib (BKM120) treatment resulted in inhibition of AKT and S6 phosphorylation and durable response in a lung squamous cell carcinoma patient-derived xenograft (PDX) model harboring PIK3CA E542K and PTEN loss (PMID: 30093452). | 30093452 |
| PTEN loss TP53 loss | prostate cancer | sensitive | Capivasertib | Preclinical | Actionable | In a preclinical study, treatment with AZD5363 improved overall survival and progression-free survival in mouse models of prostate cancer with inactivated PTEN and TP53 (PMID: 26910118). | 26910118 |
| PIK3CA E545K PTEN loss | stomach cancer | unknown | Sirolimus | Phase 0 | Actionable | In a pilot clinical trial, Rapamune (sirolimus) demonstrated modest clinical activity in patients with PIK3CA-mutant gastric cancer (n=3) or hilar cholangiocarcinoma (n=1), including 2 gastric cancer patients harboring PIK3CA E545K and PTEN loss, with a 0% response rate, median progression-free survival of 1.9 months, and median overall survival of 3.6 months (PMID: 28685070). | 28685070 |
| BRAF V600E/K PTEN loss | Advanced Solid Tumor | predicted - sensitive | PX-866 + Vemurafenib | Phase I | Actionable | In a Phase I trial, the combination therapy of PX-866 and Zelboraf (vemurafenib) demonstrated safety and resulted in an objective response in 28% (5/18) of advanced solid tumor patients harboring BRAF V600E or K, and of those five patients, 80% (4/5) also demonstrated loss of PTEN (PMID: 29051322). | 29051322 |
| CDKN2A loss PIK3CA E542K PTEN loss | lung squamous cell carcinoma | sensitive | Buparlisib + Palbociclib | Preclinical - Pdx | Actionable | In a preclinical study, treatment with the combination of Buparlisib (BYL719) and Ibrance (palbociclib) resulted in increased tumor growth inhibition compared to either agent alone in a patient-derived xenograft (PDX) model of lung squamous cell carcinoma harboring PIK3CA E542K and PTEN loss, with p16 (CDKN2A) loss (PMID: 30093452). | 30093452 |