PTEN-L

Additionally, DADS mitigated the DJ-1-associated drug resistance. The current study revealed that DJ-1 is one of potential targets for DADS, which hopefully provides a promising strategy for prevention and adjuvant chemotherapy of GC.

csi-miR-96-5p delivered by CsEVs reduced ferroptosis by regulating the expression of the PTEN/SLC7A11/GPX4 axis, thereby promoting ICC proliferation and migration. For the first time to our knowledge, we found that CS miRNAs could promote tumor development through ferroptosis.

297 pts were included: 125 treated with ADT + docetaxel (ADT+D), 79 with androgen deprivation therapy (ADT) + abiraterone or enzalutamide (A/E) and 93 with ADT alone. Lower expression of PTEN correlates with a distinct molecular profile and a more aggressive disease in pts with mHSPC, supporting the development of new therapeutic strategies in pts.

Results 218 pts were included: 125 treated with ADT + docetaxel (D) and 93 with ADT, with a median follow-up of 46 months (7-223)...Moreover, PTEN-low pts treated with ADT+D or ADT presented similar CRPC-FS (12.1 and 14.6 m, respectively) or OS (38.8 and 41 m), while PTEN-high/mid treated with ADT+D had the largest CRPC-FS (21.9 m, p=0.01) and OS (60.1 m, p=0.032), suggesting that PTEN-low pts may not benefit from chemotherapy. Conclusions Lower expression of PTEN correlates with a distinct molecular profile and a more aggressive disease in pts with mHSPC, supporting the development of new therapeutic strategies for these pts.

This study demonstrated the effect of CNV on PTEN expression and the negative immune correlation of PTEN, and constructed a classification model related to the expression of PTEN, which was of guiding significance for evaluating prognostic results of HCC patients and ICB treatment response of cancer immunotherapy cohorts.

Importantly, treatment of mice bearing Pten-null tumors with TLR agonists and anti-TGF-β antibody aimed to alter this immunosuppressive microenvironment led to tumor rejection and immunological memory in 100% of mice. These results demonstrate that lack of PTEN causes immunotherapy resistance in LUSC by establishing an immunosuppressive tumor microenvironment that can be reversed therapeutically.

ConclusionOur results demonstrate that lack of PTEN participates in IT resistance in NSCLC. Besides, we have shown that reducing Tregs in combination with an induction of a local inflammatory response is an alternative strategy to overcome α-PD-1 resistance in this context.

While phosphomimetic S380 drives neoplastic growth in prostate by promoting nuclear accumulation of β-catenin, nonphosphorylatable S380 is not tumorigenic. These data suggest that C-tail hyperphosphorylation creates oncogenic PTEN and is a potential target for anti-cancer therapy.

PIK3CA mutations are associated with resistance to NAC but do not affect the response to NAE. Low PTEN expression does not affect response to either NAC or NAE but correlates with shorter RFS in patients who received NAC. These biomarkers will be further evaluated for clinical use to treat postmenopausal luminal breast cancer patients.

218 pts were included: 125 treated with ADT + docetaxel (ADT+D) and 93 with ADT... Our results suggest that a TSGlow expression may predict the lack of benefit to taxanes in mHSPC pts, which may be useful to personalize the treatment. >

Importantly, treatment of mice bearing Pten-null tumors with TLR agonists+anti-TGF-β, aimed to alter this isTME, led to tumor rejection and immunological memory in 100% of mice. Our results demonstrate that lack of PTEN causes immunotherapy resistance in LUSC by establishing an isTME that can be reversed therapeutically.

In summary, our study showed the importance of the PTEN gene and its correlation with immunity and autophagy in HCC. The PTEN-autophagy.RS model we established could be used to predict the prognosis of HCC patients and showed significantly higher prognostic accuracy than the TIDE score in response to immunotherapy.

The stromal features of PTEN mutated breast cancer is different than that of the wild type. PTEN mutated breast cancer is associated with increased MSR. While PSA is quantitatively associated with disease specific survival in wild type and mutant breast tumors, MSR acts as a prognostic signature unique to PTEN mutated breast tumors.

P2, N=88, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2022 --> Dec 2023

The stromal features of PTEN mutated breast cancer is different than that of the wild type. PTEN mutated breast cancer is associated with increased MSR. While PSA is quantitatively associated with disease specific survival in wild type and mutant breast tumors, MSR acts as a prognostic signature unique to PTEN mutated breast tumors.

PTEN regulates pNET invasiveness via DUSP19-mediated VEGFR3 dephosphorylation. VEGFR3 and DUSP19 are potential therapeutic targets for pNET treatment.

P2, N=88, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Sep 2022 --> Dec 2022

Decreased PTEN expression in SBC, at the protein and gene levels, is associated with reduced PFS. PTEN knockdown in chordoma cells led to enhanced proliferation and invasiveness.

Quantitative PCR (qPCR) and immunohistochemical (IHC) analysis were used to detect predicted target genes. Therefore, we revealed that the PTEN-related LINC00460/miR-150-3p axis based on ceRNA mechanism plays an important role in the development of LUAD and provides a new direction and theoretical basis for its targeted therapy.

PTEN low expression/gene loss is an independent significant prognostic factor and a promising component to strengthen the clinical prognostic tools in patients with localized GIST.

Furthermore, we demonstrated that repression of PTEN by miR-96-5p increased cell proliferation and migration in sunitinib-treated cell lines. These results highlight the direct suppression of PTEN by miR-96-5p and that high miR-96-5p and low PTEN are partially responsible for sunitinib resistance and poor prognosis in CCRCC.

Systemic decrease or deletion of PTEN in the organism or organ/tissue microenvironment was conducive to the proliferation of breast cancer cells in situ and distant metastasis. These results suggest that, as well the PTEN in cancer cells the systemic microenvironment PTEN intensely mediates the proliferation, invasion and metastasis of mouse breast cancer cells via regulating the PI3K-Akt signaling pathway.

Additional data are needed to explore the underlying molecular mechanisms. Together these results further support the exploration of the impact of combining AR and PI3K signaling inhibitors in late-stage prostate cancer patients.

Low PTEN expression and high methylation of its promoter (sequence - 819 to - 787 bp) in tissue predict poor DFS and OS in hormone receptor-positive early BC patients who received adjuvant TAM.

Moreover, a consequential pairing of miR-25 with a target region in phosphatase and tensin homolog (PTEN) 3' untranslated region (UTR) and actually low PTEN expression seemed to be associated with high miR-25 (P = 0.001) in young patients. The interaction of miR-25 and PTEN in young LUAD may define a subgroup of patients, highlighting the concept of molecular testing in different age subtypes.

Regarding the remainder biomarkers, this new immunohistochemical features were found, in particular p16 and PTEN low expression in multicomponent pattern; and Ki67, hTERT and Cav.3.1 high expression in CR/PG. In conclusion, histopathology and dermoscopy provide complementary information regarding the biology of melanocytic naevi.

P2, N=88, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Sep 2021 --> Sep 2022

The combined analysis of PTEN, HER2, and HR status offers relevant information for a more precise risk assessment of patients with breast cancer.

In conclusion, decreased expression of PTEN at the protein level is seen in almost half of breast cancer patients. We found a positive correlation between PTEN protein expression with HR and HER2 status and by the decreased relative expression of PTEN, both HR- and HER2 overexpression/amplification were significantly related to worse OS compared to the HR+/HER2- status. Moreover, this HER2 positivity either alone or concomitantly with HR positivity was associated with poorer survival compared to the HR+/HER2- status.

miR-520b inhibited PTEN and aggravated breast tumors. miR-520b inhibitor enhanced CD4 and CD8 cell populations in the tumor immune microenvironment and inhibited tumor growth.

Automatic PTEN scoring was strongly predictive of the PTEN status assessed by human experts (area under the curve 0.987 (95% CI 0.968 to 0.994)). This suggests that PTEN status can be accurately assessed using ML, and that the combined marker of automatically assessed PTEN and DNA ploidy status may provide an objective supplement to the existing risk stratification factors in prostate cancer.

In this study, negative ERG expression was strongly associated with immediate biochemical progression after radical prostatectomy. Moreover, a trend towards a relationship between aberrant PTEN expression and progression was observed. Additional studies with long-term follow up data may provide further clinical insight into the genomic heterogeneity in this population.

Final OS results show a numerical trend favoring ipatasertib-paclitaxel and median OS exceeding 2 years with ipatasertib-paclitaxel. Overall, results are consistent with the reported PFS benefit; interpretation within biomarker-defined subgroups is complicated by small sample sizes and TNBC heterogeneity.

This clinical impact was observed in the less aggressive CLL subtype with mutated IGHV in which high ENDOG and low PTEN levels were associated with worse outcome. In summary, our results show that reducing ENDOG expression hinders growth of some tumors characterized by low PTEN activity and high p-AKT expression and that ENDOG has prognostic value for some cancer types.

Lower ATM intensity is associated with increased cancer-specific mortality in prostate cancer patients. Patients with lower ATM and PTEN negative expression showed decreased overall survival and increased cancer mortality compared with controls.

High Amphiregulin and PTEN expression levels and low P21 expression levels were associated with better response to anti-EGFR therapy and improved survival outcome. They might be considered predictive markers of response to anti-EGFR therapy in mCRC. .

 The combined analysis of PTEN protein and gene expression may provide additional data to perform a tailored risk assessment while evaluating patients with HR- and HER2+ breast cancers.

This study identified PTEN-low/RhoA-signalling-high, and high AKT1 and PD1 expression as potent prognostications for BL1, BL2 and IM subtypes with survival differences of over 14, 2.75 and 10.5 years, respectively. This intrinsic heterogeneity could be exploited to prioritize patients for precision medicine.

The addition of copanlisib to gemcitabine and cisplatin does not improve PFS at 6 months. However, future studies using PTEN as a potential biomarker should be considered.

There is a strong association between TRPV1 and PTEN and the combination of TRPV1 and PTEN is a strong indicator of prognostic predictor in EOC.

AKBA inhibits the proliferation and migration and promotes the apoptosis of gastric cancer cells through the PTEN/Akt/COX-2 signaling pathway.

Co-expression of PTEN/pAkt and pAkt phenotypes was associated with a less favorable overall survival (P=0.001). Overall, the present findings demonstrated that low expression levels of PTEN and high expression levels of pAkt and pAkt were predictors for poor overall survival in patients with UTUC.