BRCA mutation

Our findings establish MAP3K1 and MAP2K4 as key tumor suppressors in BRCA that operate via the JNK2-p53-FOSL1 axis. Their inactivation provides an alternative mechanism for p53 pathway disruption, adhering to the "minimal necessary alteration" principle in cancer signaling. This study highlights the dual regulatory mechanisms controlling FRA1 expression and offers insights into breast cancer heterogeneity, with potential implications for targeted therapy and patient stratification.

PARPi + NHA represent a significant advance in mCRPC therapy. Molecular genetic testing for HRR mutations, especially BRCA 1/2, is crucial for treatment planning.

To overcome foundation model constraints, approaches like model distillation, weak supervision, and modular training are critically examined. Progress now depends on high-quality datasets, rigorous multi-institutional validation, and collaboration between computational scientists, clinicians, and regulators to deliver explainable, clinically actionable innovations in breast cancer.

The present findings are from a limited number of heterogenous studies and hence must be interpreted with caution. https://www.crd.york.ac.uk/prospero/, identifier CRD42025641361.

A total of 44 manuscripts were retrieved, with only two articles reporting data on pregnancy with vitrified oocytes after fertility-sparing surgery, and 3 cases included. Whilst more research is required for assisted reproductive technology and ovarian cancer, and for the elucidation of the role of BRCA mutations on fertility, the present report aims to provide impetus to further research in this field.

This benefit was confirmed in a multivariable analysis, supporting PARPi as the preferred option in eligible patients. Our findings suggest that PARPi should be prioritized in the post-CDK4/6i treatment sequence for BRCA LP/PV carriers with HR+/HER2 aBC and highlight the critical role of germline BRCA testing.

Targeted agents did not demonstrate a significant clinical benefit in mesothelioma treatment, nevertheless a small group of patients might harbor potentially actionable somatic mutations, as in homologous repair recombination genes. In this paper we report two cases of patients with heavily pretreated pleural mesothelioma that had a relevant clinical benefit with rucaparib treatment based on somatic BRCA 1 and BRCA 2 mutations detected through next generation sequencing.

WEE1 inhibitors have shown encouraging results in combination with chemotherapy, increasing the objective response rate in patients with platinum-resistant TP53-mutated ovarian cancer. ATR inhibitors are currently being evaluated in ARID1A-mutated tumours, with preliminary results confirming their therapeutic potential.

No significant differences in recurrence pattern or survival outcome were observed between CRS with HIPEC and CRS alone. However, distinct recurrence patterns observed in BRCA-mutated patients suggest potential biological differences that may influence treatment outcomes. A trend toward reduced gastrointestinal morbidity in the HIPEC group, potentially reflecting a more subtle, less invasive recurrence pattern. Further research is warranted to elucidate these observations.

DUO-O met its primary PFS endpoints for first-line durvalumab plus carboplatin/paclitaxel and bevacizumab followed by durvalumab, bevacizumab plus olaparib maintenance versus carboplatin/paclitaxel and bevacizumab followed by bevacizumab in the non-tBRCAm HRD-positive and non-tBRCAm ITT populations. Further insight into long-term benefit is anticipated with additional follow-up.

We review the current FDA approvals that now prioritize patients with BRCA-mutated and HRD ovarian cancers, underscoring the importance of biomarker stratification and careful patient selection. We discuss the evolving regulatory landscape and potential mechanisms of PARPi resistance.

The authors emphasize the importance of integrating radiologic findings with clinical context, with the aim enhancing awareness and expertise in the detection and characterization of gynecologic manifestations associated with hereditary syndromes, thereby contributing to optimal patient management.