BRCA wild-type

Consequently, BRCA2 and Rad51 were then ubiquitinated and degraded to inhibit HR and increase the sensitivity of OC to PARPi. Thus, these findings reveal that the combination of 4C with PARPi leading to "synthetic lethality" is an effective strategy for treating BRCA1/2 wild-type OC.

SLFN11 enhances PARPi sensitivity in EOC by stabilizing PARP1/2 via inhibition of proteotoxic ubiquitination, supporting its role as a biomarker in a BRCA-wild-type EOC cell model where PARPi efficacy is limited by intrinsic resistance. While the application of PARPi in other subtypes of EOC still requires further validation, SLFN11 may improve PARPi response and could be explored as a strategy to address PARPi resistance.

EOC patients with gBRCA-m experienced earlier and more severe CIM, highlighting the need for careful monitoring and tailored management.

P2, N=45, Not yet recruiting, The First Affiliated Hospital of Soochow University

HRD status is a prognostic biomarker in HGSC. Its correlation with SET patterns supports histology as an initial screening tool. Importantly, NACT is correlated with reduced detectable HRD positivity and lower GSS, underscoring the need for HRD testing before chemotherapy to ensure accurate assessment and guide treatment.

Herein, a series of novel c-Met/PARP dual-target inhibitors based on the moiety of Olaparib were designed and synthesized...In particular, L19 exhibited good in vivo antitumor activity (tumor growth inhibition (TGI) rate = 32%) in MDA-MB-231 xenograft models with low toxicity. Taken together, our designed dual c-Met/PARP inhibitors are novel and promising agents for the treatment of BRCA wild-type TNBC.

Overall, the results indicate that maintaining Abiraterone treatment in combination with PARPis after resistance develops provides superior therapeutic efficacy compared to PARP inhibition alone, offering a promising strategy for managing Abiraterone-resistant prostate cancer. Combining Abiraterone with PARPis enhances therapeutic efficacy and overcomes the acquired insensitivity in mCRPC with BRCA1/2 or HRR mutations. These results support continued use of PARPis with Abiraterone to improve clinical outcomes.

In an HCT116 xenograft model, I-16 (20 mg/kg) elicited significant tumor growth suppression, outperforming Olaparib (50 mg/kg) or BVD-523 (5 mg/kg) monotherapy and achieving efficacy comparable to their combination. These findings suggest that I-16, as the first potent dual PARP1/ERK inhibitor, represents a promising candidate for cancer therapy.

Progesterone enhances the sensitivity of ovarian cancer cells to PARP inhibitors by downregulating TRC-protective factors via mPR-mediated non-genomic actions. These in vitro findings suggest a potential preclinical rationale for combining progesterone with PARP inhibitors in BRCA-wild-type ovarian cancer; in vivo validation and dosing studies are needed before clinical consideration.

Moreover, the study enhanced the role of healthy glandular tissue in distinguishing the two groups, supporting and reinforcing previous MRI-based radiomics findings in the same population. The study concludes that radiomics analysis of diagnostic mammograms in TNBC patients is feasible and may help build predictive models to discriminate between BRCA mutated and non-mutated patients.

Multivariate Cox regression analysis identified clinical stage as an independent predictor of overall survival, with patients at stages Ⅲ-Ⅳ exhibiting poorer prognosis (HR=5.359, 95% CI: 1.124-25.546). BRCA-mutated colorectal tumors exhibit lower invasiveness, higher TMB-H rates, and abundant immune cell infiltration in the tumor microenvironment, suggesting that patients with BRCA-mutated colorectal cancer are more likely to benefit from immunotherapy.

A significant improvement in overall survival was observed in those who underwent primary cytoreductive surgery, regardless of first-line poly (adenosine diphosphate-ribose) polymerase inhibitor maintenance. Long-term disease-free survivors (>10 years) were only identified in the primary cytoreductive surgery cohort.