Molecular Profile |
Indication/Tumor Type |
Response Type |
Therapy Name |
Approval Status |
Evidence Type |
Efficacy Evidence |
References |
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
|
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
|
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
|
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
|
triple-receptor negative breast cancer
|
predicted - sensitive
|
Capivasertib + Paclitaxel
|
Phase II |
Actionable |
In a Phase II trial (PAKT), addition of Capivasertib (AZD5363) 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
|
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
|
castration-resistant prostate carcinoma
|
predicted - sensitive
|
CC-115 + Enzalutamide
|
Phase I |
Actionable |
In a Phase Ib trial, Xtandi (enzalutamide) and CC-115 combination therapy was safe and resulted in a PSA reduction >= 50% (PSA50) in 80% (32/40) and >=90% (PSA90) in 58% of patients with metastatic castration-resistant prostate cancer at 12 weeks, patients harboring PTEN mutation or deletion (n=11) achieved superior PSA50, PSA90, and median time on treatment (91%, 55%, 59 wks) compared to PTEN wild-type (n=29) patients (76%, 59%, 44 wks) (Ann Oncol (2021) 32 (suppl_5): S626-S677; NCT02833883).
|
detail...
|
PTEN inact mut
|
Advanced Solid Tumor
|
sensitive
|
Capivasertib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, AZD5363 inhibited growth of various solid tumor cell culture models with inactivating Pten mutations (PMID: 22294718).
|
22294718
|
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
|
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
|
triple-receptor negative breast cancer
|
no benefit
|
Ipatasertib + Paclitaxel
|
Phase III |
Actionable |
In a Phase III trial (IPATunity 130), the addition of Ipatasertib (GDC-0068) to treatment with Abraxane (paclitaxel) did not result in improved progression-free survival in patients with triple-negative breast cancer harboring PIK3CA and/or AKT activating mutations or PTEN alterations, with a median PFS of 7.4 months with Ipatasertib (GDC-0068) plus Abraxane (paclitaxel) vs. 6.1 months with placebo plus Abraxane (paclitaxel) (SABCS 2020, Abstract GS3-04; NCT03337724).
|
detail...
|
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
|
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
|
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 mutant
|
endometrial cancer
|
sensitive
|
GDC-0980
|
Phase II |
Actionable |
In a Phase II trial, Apitolisib (GDC-0980) was poorly tolerated, but demonstrated efficacy in endometrial cancer patients harboring mutations in PIK3CA, PTEN, or AKT1 (J Clin Oncol 32:5s, 2014 (suppl; abstr 5513)).
|
detail...
|
PTEN mutant
|
endometrial cancer
|
sensitive
|
A66 + AZD6482
|
Preclinical |
Actionable |
In a preclinical study, A66 and AZD6482 combination treatment inhibited viability of endometrioid endometrial cancer cell lines harboring PTEN mutations in culture (PMID: 23674493).
|
23674493
|
PTEN mutant
|
endometrial cancer
|
no benefit
|
Temsirolimus
|
Phase II |
Actionable |
In a retrospective study of a Phase II trial, mutation status of PTEN was not associated with progression-free survival or response rate in advanced endometrial cancer patients treated with Torisel (temsirolimus) (PMID: 27016228).
|
27016228
|
PTEN mutant
|
gastrointestinal system cancer
|
decreased response
|
Pembrolizumab
|
Clinical Study - Cohort |
Actionable |
In a retrospective analysis, patients with MSI high, dMMR gastrointestinal tumors including gastric (n=18), colorectal (n=17), cholangiocarcinoma (n=5), small intestine (n=2), pancreatic (n=2), and duodenal cancer (n=1) harboring PTEN mutations demonstrated a decreased objective response rate (21.4 vs 54.8%), overall survival (15.2 vs 25.7 mo), and progression-free survival (4.3 vs 15.6 mo) compared to PTEN-wild-type patients when treated with Keytruda (pembrolizumab) or Opdivo (nivolumab) (PMID: 33926917).
|
33926917
|
PTEN mutant
|
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 mutant
|
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 mutant
|
endometrial cancer
|
sensitive
|
A66 + GSK2636771
|
Preclinical |
Actionable |
In a preclinical study, A66 and GSK2636771 combination treatment inhibited viability of endometrioid endometrial cancer cell lines harboring PTEN mutations in culture (PMID: 23674493).
|
23674493
|
PTEN mutant
|
breast cancer
|
sensitive
|
Sapanisertib
|
Preclinical |
Actionable |
In a preclinical study, Sapanisertib (MLN0128) induced apoptosis and inhibited MTORC1 signaling in breast cancer cells harboring a PTEN mutation (PMID: 25261369).
|
25261369
|
PTEN mutant
|
endometrial cancer
|
sensitive
|
Everolimus
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, Afinitor (everolimus) inhibited growth of endometrial cancer cells harboring a PTEN nonsense mutation in culture and in xenograft models (PMID: 22662154).
|
22662154
|
PTEN mutant
|
uterine cancer
|
sensitive
|
GSK2256098 + Paclitaxel
|
Preclinical |
Actionable |
In a preclinical study, uterine cancer cells harboring a PTEN mutation were more sensitive to the combination of GSK2256098 and Taxol (paclitaxel) than uterine cancer cells wild-type for PTEN, resulting in decreased tumor growth in culture and in mouse models (PMID: 25833835).
|
25833835
|
PTEN mutant
|
Advanced Solid Tumor
|
no benefit
|
Talazoparib
|
Phase II |
Actionable |
In a Phase II trial, Talzenna (talazoparib) treatment did not result in significant clinical benefit in patients with advanced solid tumors harboring PTEN mutation or loss (by IHC), with one patient harboring a PTEN mutation achieved a prolonged stable disease as best response in a cohort of 13 patients (Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A096; NCT02286687).
|
detail...
|
PTEN mutant
|
lung adenocarcinoma
|
no benefit
|
Capivasertib
|
Case Reports/Case Series |
Actionable |
In a Phase II trial (NLMT), Capivasertib (AZD5363) treatment did not result in a confirmed response (0/8) or durable clinical benefit (0/8) in patients with lung adenocarcinoma harboring mutations in PIK3CA, PTEN, or AKT, thus the cohort was closed due to futility (PMID: 32669708, NCT02664935).
|
32669708
|
PTEN mutant
|
endometrial cancer
|
sensitive
|
Dactolisib
|
Preclinical |
Actionable |
In a preclinical study, BEZ235 decreased growth of endometrial cancer cells harboring a PTEN nonsense mutation in culture and in xenograft models (PMID: 22662154).
|
22662154
|
PTEN mutant
|
endometrial cancer
|
resistant
|
AZD6482
|
Preclinical |
Actionable |
In a preclinical study, endometrioid endometrial cancer cell lines harboring PTEN mutations demonstrated resistance to AZD6482 induced growth inhibition in culture (PMID: 23674493).
|
23674493
|
PTEN mutant
|
hepatocellular carcinoma
|
decreased response
|
Sorafenib
|
Clinical Study - Cohort |
Actionable |
In a clinical case study, Nexavar (sorafenib) treatment of patients with hepatocellular carcinoma harboring Mtor pathway mutations in PIK3CA, PTEN, TSC2, or TSC1 (n=12), resulted in a lower disease control rate (8.3% vs. 40.2%), shorter progression-free survival (1.9 months vs. 5.3 months) and shorter overall survival (10.4 months vs. 17.9 months) compared to patients without mutations in this pathway (n=67) (PMID: 30373752; NCT01775072).
|
30373752
|
PTEN mutant
|
skin melanoma
|
not applicable
|
N/A
|
Guideline |
Risk Factor |
Germline PTEN mutations or polymorphisms are associated with increased risk of developing single or multiple primary cutaneous melanomas (NCCN.org).
|
detail...
|
PTEN mutant
|
head and neck squamous cell carcinoma
|
resistant
|
Taselisib
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, head and neck squamous cell carcinoma cell lines and cell line xenograft models with PTEN alterations were resistant to the apoptotic effects of Taselisib (GDC-0032) (PMID: 26589432).
|
26589432
|
PTEN mutant
|
gastrointestinal system cancer
|
decreased response
|
Nivolumab
|
Clinical Study - Cohort |
Actionable |
In a retrospective analysis, patients with MSI high, dMMR gastrointestinal tumors including gastric (n=18), colorectal (n=17), cholangiocarcinoma (n=5), small intestine (n=2), pancreatic (n=2), and duodenal cancer (n=1) harboring PTEN mutations demonstrated a decreased objective response rate (21.4 vs 54.8%), overall survival (15.2 vs 25.7 mo), and progression-free survival (4.3 vs 15.6 mo) compared to PTEN-wild-type patients when treated with Keytruda (pembrolizumab) or Opdivo (nivolumab) (PMID: 33926917).
|
33926917
|
PTEN mutant
|
endometrial cancer
|
resistant
|
GSK2636771
|
Preclinical |
Actionable |
In a preclinical study, endometrioid endometrial cancer cell lines harboring PTEN mutations demonstrated resistance to GSK2636771 induced growth inhibition in culture (PMID: 23674493).
|
23674493
|
PTEN mutant
|
endometrial cancer
|
resistant
|
A66
|
Preclinical |
Actionable |
In a preclinical study, endometrioid endometrial cancer cell lines harboring PTEN mutations demonstrated resistance to A66 induced growth inhibition in culture (PMID: 23674493).
|
23674493
|
PTEN mutant
|
uterine cancer
|
sensitive
|
GSK2256098
|
Preclinical |
Actionable |
In a preclinical study, uterine cancer cells harboring a PTEN mutation demonstrated sensitivity to GSK2256098, resulting in inhibition of Ptk2 (Fak) phosphorylation, decreased tumor growth, and apoptosis both in culture and in mouse models (PMID: 25833835).
|
25833835
|
PTEN mutant
|
endometrial cancer
|
resistant
|
TGX-221
|
Preclinical |
Actionable |
In a preclinical study, endometrioid endometrial cancer cell lines harboring PTEN mutations demonstrated resistance to TGX-221 induced growth inhibition in culture (PMID: 23674493).
|
23674493
|
PTEN mutant
|
uterine cancer
|
sensitive
|
GSK2256098 + Topotecan
|
Preclinical |
Actionable |
In a preclinical study, uterine cancer cells harboring a PTEN mutation were more sensitive to the combination of GSK2256098 and Hycamtin (topotecan) than uterine cancer cells wild-type for PTEN, resulting in decreased tumor growth in culture and in mouse models (PMID: 25833835).
|
25833835
|
PTEN mutant
|
melanoma
|
sensitive
|
BI-69A11
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, BI-69A11 resulted in antitumor activity in a melanoma cell line harboring a PTEN mutation, including induction of cell death in culture, and in xenograft models, tumor growth inhibition and tumor regression (PMID: 19175524).
|
19175524
|
PTEN mutant
|
breast cancer
|
predicted - sensitive
|
MS417 + Pictilisib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, Pictilisib (GDC-0941) and MS417 in combination resulted in improved growth inhibition and increased cell death compared to either agent alone in a PTEN-mutant breast cancer cell line in culture (PMID: 26058079).
|
26058079
|