BRCA mutation

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.

We highlight the spectrum of CTNA-induced lesions and repair pathways required for cellular tolerance. This framework presents a versatile "repair-defect-guided" chemotherapy that expands the clinical utility of CTNAs and improves therapeutic effect by reducing side effects.

The patient declined BRCA genetic testing and prophylactic surgical interventions, opting to continue fertility treatment under enhanced surveillance. This unprecedented case emphasizes the critical importance of comprehensive histopathological evaluation of surgically resected fallopian tubes, even when removed for benign reproductive indications, and highlights the complex decision-making process regarding genetic counseling, surveillance strategies, and fertility preservation in reproductive-aged women with incidentally diagnosed STIC.

Our study demonstrated modest clinical benefits of D + O with ORR of 28.6% in subsets of heavily pretreated TNBC. Further detailed classification of DCs to understand the predictive role of DCs and prospective validation in a large cohort is required.

We evaluated cell cycle-targeted strategies to overcome HR-proficient chemoresistance using either volasertib (a selective PLK1 inhibitor) or adavosertib (a potent WEE1 inhibitor) in BRCA-WT/HR-proficient and BRCA-mutant/HR-deficient HGSOC models. Functional and xenograft models confirmed selective vulnerability of BRCA-WT tumors to either PLK1 or WEE1 inhibition. Our work highlights a mechanistic framework linking cell cycle checkpoint inhibition to DNA repair pathway selectivity, providing a rationale for targeting mitotic regulators in HR-proficient ovarian cancer-a subgroup with high clinical unmet need.

Importantly, we find that the loss of EP300 results in decreased expression of BRCA2 protein leading to sensitivity to treatments that are cytotoxic to BRCA-deficient cancers. Overall, we demonstrate that EP300-mutated cells recapitulate features of BRCA-deficient cancers.