PTEN-L

Erastin-mediated inhibition of SCL7A11 induced ferroptosis in cells with ELF3 overexpression and PTEN deficiency and thus inhibited cell colony formation and tumor development...ELF3 and SCL7A11 expression levels were negatively associated with lung cancer patients' survival rates. In summary, ferroptosis induction can effectively attenuate lung tumor development induced by ELF3 overexpression and PTEN downregulation or loss-of-function mutations.

This study explores the prognostic and predictive role of PIK3CA hotspot mutations in low-risk postmenopausal breast cancer patients randomized to receive tamoxifen or no systemic treatment, followed for over 25 years with extensive clinical records...In conclusion, PIK3CA mutations predominate within the ER+/HER2- subtype, are associated with good clinical markers, and longer DRFI in all patients, especially among highly proliferative and high-risk tumors, but not within ultralow risk patients. Ongoing investigation aims to decipher other factors associated with PIK3CA mutations in patients with indolent tumors who present long-term relapses and may take advantage of new treatment strategies.

Datasets analysis of NSCLC patients revealed that PTEN expression is negatively correlated to YAP/TAZ, EZH2 and MYC and that low expression of PTEN is predictive of poor prognosis, especially at earlier stages of the disease. These findings highlight the repressive role of the YAP/TAZ-EZH2-MYC axis on tumor-suppressor genes and offer a potential therapeutic strategy for lung cancer patients with low PTEN levels.

Low PTEN expression (s-score of 6 or less) was used as a diagnostic criterion for high-grade PTs, it showed 100 % sensitivity and 95.2 % specificity in 42 cases of PTs. Currently, PT grading based solely on subjective histologic findings is challenging, but semiquantitative PTEN expression analysis could provide a more accurate and objective way to grade PTs.

Low PTEN expression is a significant predictor of biochemical recurrence in patients with castration-sensitive PCa who have already undergone prostatectomy.

Fifteen miRNAs from 17 studies were found, and together with PTEN expression, they may serve as potential prognostic biomarkers for OSC. High-level levels of miRNA expression are correlated with low PTEN expression, leading to a bad prognosis for OSC.

Considering the recent approval of capivasertib for HR+/HER2- metastatic breast cancer (MBC) harboring PI3K-AKT pathway alts based on tissue NGS, we assessed the concordance of tissue and ctDNA NGS for PIK3CA, AKT1, PTEN as well as ESR1. We identified 367 HR+/HER2- MBC pts treated at MSK with tissue NGS by MSK-IMPACT within 60 days of ctDNA NGS by either Guardant360 or MSK-ACCESS, without intervening therapy... Tissue-ctDNA concordance for the detection of any oncogenic alteration was high for PIK3CA, AKT1, moderate for ESR1, and low for PTEN. More alts were detected in ctDNA for ESR1 and in tissue for PTEN, reflecting acquired ESR1 alts after estrogen deprivation and the current lack of ctDNA assay PTEN copy number loss detection. Additional correlative analyses (e.g.

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.