PTEN inact mut: Gene Variant Detail - Cancer Knowledgebase (CKB)

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Showing 1 to 25 of 25 entries

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
PTEN inact mut	triple-receptor negative breast cancer	no benefit	Ipatasertib + Paclitaxel	Phase III	Actionable	In a Phase III trial (IPATunity130), the addition of Ipatasertib (GDC-0068) to treatment with Abraxane (paclitaxel) did not result in improved median progression-free survival (7.4 mo vs 6.1 mo, HR=1.02, p=0.92), median overall survival (24.4 mo vs 24.9 mo, HR=1.08), objective response rate (39% vs 35%) or clinical benefit rate (47% vs 45%) in patients with metastatic triple-negative breast cancer harboring PIK3CA and/or AKT activating mutations or PTEN inactivating mutations (PMID: 39058425; NCT03337724).	39058425
PTEN inact mut	triple-receptor negative breast cancer	predicted - sensitive	Capivasertib + Paclitaxel	Phase II	Actionable	In a Phase II trial (PAKT), addition of Truqap (capivasertib) to Taxol (paclitaxel) as first-line therapy significantly improved median progression-free survival (9.3 vs 3.7 months, HR=0.30, p=0.01) and reduced risk (66%, HR=0.34, p=0.04) compared to Taxol (paclitaxel) alone in patients with metastatic triple-negative breast cancer harboring activating mutations in AKT1 (n=1) or PIK3CA (n=17), or inactivating mutations or gene loss in PTEN (n=13) (PMID: 31841354; NCT02423603).	31841354
PTEN inact mut	triple-receptor negative breast cancer	no benefit	Ipatasertib + Paclitaxel	Phase II	Actionable	In a Phase II trial (LOTUS), Ipatasertib (GDC-0068) in combination with Abraxane (paclitaxel) resulted a median progression free survival of 6.2 vs 4.9 months with placebo in triple-receptor negative breast cancer patients harboring activating mutations in PIK3CA or AKT1, or inactivating mutations in PTEN (PMID: 28800861; NCT02162719).	28800861
PTEN inact mut	endometrial cancer	no benefit	LY3023414	Phase II	Actionable	In a Phase II trial, patients with advanced endometrial cancer harboring a PI3K pathway mutation, including PTEN inactivating mutations, demonstrated only a modest clinical benefit with an overall response rate of 16% (4/25), a clinical benefit rate of 28% (7/25) at 12 weeks, a progression-free survival of 2.5 months, and overall survival of 9.2 months when treated with LY3023414 (PMID: 31880826; NCT01775072).	31880826
PTEN inact mut	Advanced Solid Tumor	predicted - sensitive	Temsirolimus	Phase II	Actionable	In a Phase II trial (TAPUR), Torisel (temsirolimus) treatment resulted in a disease control rate of 26% (7/27, 2 partial responses and 5 with stable disease >=16 weeks) and an objective response rate of 7% (2/27) in patients with advanced solid tumors harboring inactivating PTEN mutations, with a median progression-free survival of 10 weeks and a median overall survival of 32 weeks (Cancer Res (2023) 83 (8_Supplement): CT231; NCT02693535).	detail...
PTEN inact mut	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 inact mut	Advanced Solid Tumor	predicted - sensitive	Copanlisib + Nivolumab	Phase II	Actionable	In a Phase II trial (BaCoN), treatment with the combination of Aliqopa (copanlisib) and Opdivo (nivolumab) was well tolerated in patients with advanced solid tumors harboring an inactivating mutation in PTEN, and resulted in a complete response/partial response (CR/PR) in 20% (3/15, 3 cPR) and a clinical benefit rate (CR or PR or stable disease > 4 months) of 33% (Ann Oncol 34 (2023): S487-S488; NCT04317105).	detail...
PTEN inact mut	Advanced Solid Tumor	no benefit	Talazoparib	Phase II	Actionable	In a Phase II trial, Talzenna (talazoparib) treatment resulted in limited clinical benefit in patients with advanced solid tumors harboring PTEN deleterious mutations or loss (by IHC), with a clinical benefit rate of 9.4% (1/14, 1 with stable disease >/=24 weeks) and a median overall survival of 8.5 months and a median progression-free survival of 7.7 weeks (PMID: 39085400; NCT02286687).	39085400
PTEN inact mut	Advanced Solid Tumor	no benefit	Copanlisib	Phase II	Actionable	In a Phase II trial (NCI-MATCH subprotocol Z1H), Aliqopa (copanlisib) treatment demonstrated limited efficacy in patients with advanced solid tumors harboring PTEN inactivating mutations, with an objective response rate of 3.4% (1/29, 1 partial response in a patient with endometrioid endometrial adenocarcinoma), stable disease in 28% (8/29) of patients, median progression-free survival (PFS) of 1.8 mo, 6-mo PFS rate of 15.4%, and median overall survival of 9.0 mo (PMID: 39913886; NCT02465060).	39913886
PTEN inact mut	castration-resistant prostate carcinoma	predicted - sensitive	CC-115 + Enzalutamide	Phase I	Actionable	In a Phase Ib trial, Xtandi (enzalutamide) plus CC-115 was safe and led to a PSA reduction >= 50% (PSA50) in 80% (32/40) and >=90% (PSA90) in 58% (23/40) of patients with metastatic castration-resistant prostate cancer at 12 weeks, and patients harboring PTEN mutation or deletion (n=11) achieved PSA50 of 91%, PSA90 of 55%, and median radiographic progression-free survival was not reached, compared to 75%, 55%, and 19.6 mo, respectively, in PTEN wild-type patients (n=20) (PMID: 37980367; NCT02833883).	37980367
PTEN inact mut	glioblastoma	predicted - sensitive	Atezolizumab + Ipatasertib	Phase I	Actionable	In a Phase I trial (Ice-CAP), combination treatment with Ipatasertib (GDC-0068) and Tecentriq (atezolizumab) demonstrated safety and tolerability in glioblastoma patients harboring PTEN loss or PTEN mutations, and led to a clinical benefit rate of 29% (2/7), with 1 pathological complete response, and stable disease in 1 patient of 7 patients (Cancer Res 2021;81(13_Suppl):Abstract nr CT120; NCT03673787).	detail...
PTEN inact mut	lung non-small cell carcinoma	predicted - resistant	Osimertinib	Case Reports/Case Series	Actionable	In a retrospective analysis, inactivating PTEN mutations were identified in 3 of 100 patients with non-small cell lung cancer at treatment discontinuation of Tagrisso (osimertinib) (PMID: 31839416).	31839416
PTEN inact mut	head and neck cancer	predicted - sensitive	RMC-5552	Case Reports/Case Series	Actionable	In a Phase I/Ib trial, RMC-5552 treatment resulted in an objective response rate of 20% (1/5) and 3 stable disease in patients with advanced solid tumors, with 1 partial response observed in a patient with head and neck cancer harboring a pathogenic PTEN mutation (J of Clin Oncol40, no. 16_suppl (June 01, 2022) 3098; NCT04774952).	detail...
PTEN inact mut	breast cancer	predicted - sensitive	TAS-117	Case Reports/Case Series	Actionable	In a Phase II trial, TAS-117 treatment demonstrated tolerability in patients with advanced solid tumors harboring germline inactivating PTEN mutations, and resulted in an unconfirmed partial response in one patient with breast cancer and target tumor lesion shrinkage of approximately 15% and stable disease lasting more than 8 months in another breast cancer patient (Ann Oncol (2022) 33 (suppl_7): S754-S755; NCT04770246).	detail...
PTEN inact mut	Advanced Solid Tumor	no benefit	LY3023414	Case Reports/Case Series	Actionable	In a Phase II trial (NCI-COG Pediatric MATCH), Samotolisib (LY3023414) treatment resulted in no objective responses in pediatric patients with advanced solid tumors harboring PI3K/mTOR pathway mutations, including PTEN (n=6), PIK3CA (n=5), TSC1 (n=2), TSC2 (n=3), and PIK3R1 (n=1), and resulted in a 3-month progression-free survival of 12%, a 6-month overall survival of 44%, and a 12-month overall survival of 15% (PMID: 39298693; NCT03155620).	39298693
PTEN inact mut	prostate adenocarcinoma	sensitive	XL147	Preclinical - Cell line xenograft	Actionable	In a preclinical study, XL147 inhibited PI3K signaling, growth, and migration of a human prostate adenocarcinoma cell line harboring a PTEN inactivating mutation in culture, and inhibited tumor growth and vascularization in xenograft models (PMID: 25637314).	25637314
PTEN inact mut	prostate adenocarcinoma	sensitive	Paclitaxel + XL147	Preclinical - Cell line xenograft	Actionable	In a preclinical study, the combination of XL147 and Taxol (paclitaxel) inhibited tumor growth and angiogenesis in xenograft models of a human prostate adenocarcinoma cell line harboring an inactivating mutation in PTEN, with increased efficacy compared to either agent alone (PMID: 25637314).	25637314
PTEN inact mut	kidney cancer	sensitive	LY3023414	Preclinical - Cell line xenograft	Actionable	In a preclinical study, LY3023414 inhibited proliferation of renal cancer cells harboring PTEN inactivating mutation in culture, resulted in tumor growth inhibition in cell line xenograft models (PMID: 27439478).	27439478
PTEN inact mut	glioblastoma	sensitive	Voxtalisib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, a glioblastoma cell line harboring a PTEN inactivating mutation was sensitive to XL765 (SAR245409), demonstrating inhibition of cell proliferation in culture, and inhibition of tumor growth in cell line xenograft models (PMID: 24634413).	24634413
PTEN inact mut	glioblastoma	sensitive	SF1126	Preclinical - Cell line xenograft	Actionable	In a preclinical study, a glioblastoma cell line harboring a PTEN inactivating mutation (PMID: 24634413) was sensitive to SF1126, demonstrating inhibition of tumor growth in cell line xenograft models (PMID: 18172313).	18172313 24634413
PTEN inact mut	breast cancer	predicted - sensitive	AZD5991 + AZD8186	Preclinical - Cell line xenograft	Actionable	In a preclinical study, the combination of AZD5991 and AZD8186 synergistically inhibited proliferation and induced apoptosis in a triple-negative breast cancer cell line and hormone receptor-positive breast cancer cell line each harboring a PTEN inactivating mutation in culture and inhibited tumor growth in cell line xenograft models (PMID: 36241868).	36241868
PTEN inact mut	breast cancer	predicted - sensitive	AZD5991 + Capivasertib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, the combination of AZD5991 and Truqap (capivasertib) synergistically inhibited proliferation and induced apoptosis in a triple-negative breast cancer cell line and hormone-receptor positive breast cancer cell line each harboring a PTEN inactivating mutation in culture and inhibited tumor growth in cell line xenograft models (PMID: 36241868).	36241868
PTEN inact mut	estrogen-receptor positive breast cancer	sensitive	Pictilisib	Preclinical - Cell culture	Actionable	In a preclinical study, a PTEN deficient estrogen-receptor (ER) positive breast cancer cell line demonstrated increased sensitivity to treatment in culture when Pictilisib (GDC-0941) was given at a higher dose for a shorter duration, resulting in inhibition of cell growth (PMID: 26733612).	26733612
PTEN inact mut	estrogen-receptor positive breast cancer	sensitive	Fulvestrant + Pictilisib	Preclinical - Cell culture	Actionable	In a preclinical study, the combination of Faslodex (fulvestrant) and PIctilisib (GDC-0941) resulted in decreased cell viability and increased apoptotic activity in PTEN deficient estrogen-receptor (ER) positive breast cancer cells in culture (PMID: 26733612).	26733612
PTEN inact mut	Advanced Solid Tumor	sensitive	Capivasertib	Preclinical - Cell culture	Actionable	In a preclinical study, Truqap (capivasertib) inhibited growth of various solid tumor cell culture models with inactivating Pten mutations (PMID: 22294718).	22294718

Showing 1 to 25 of 25 entries

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Gene	PTEN
Variant	inact mut
Impact List	unknown
Protein Effect	loss of function
Gene Variant Descriptions	PTEN inact mut indicates that this variant results in a loss of function of the Pten protein. However, the specific amino acid change has not been identified.
Associated Drug Resistance
Category Variants Paths	PTEN mutant PTEN inact mut

PTEN inact mut
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PTEN inact mut
Gene Variant Detail