HRD (Homologous Recombination Deficiency)

In addition, SGO2 compromised the cisplatin (CDDP) sensitivity of LUAD in vitro and in vivo...Silencing SGO2 with OA improved LUAD chemo sensitivity. Our work highlights the potential of SGO2 as a target for therapeutic intervention and OA as a food-bioactive compound for LUAD treatment.

In vitro and in vivo studies demonstrated enhanced radiosensitization, robust inhibition of RAD51-mediated repair, prolonged intratumoral retention plausibly driven by platelet-like geometry, and minimal systemic toxicity. These results establish HfNPs as a high-Z radiosensitizing platform that improves radiotherapeutic outcomes through both enhanced physical energy deposition and biochemical blockade of damage repair, with nanoplatelet dimensionality presenting an opportunity to further strengthen these effects.

We systematically deconstructed the molecular subtypes of primary GISTs by integrated genomic and transcriptomic analysis. A specific GIST subtype characterized by poor treatment responses and prognosis, marked by the activation of aerobic metabolism and HRD features, may be a potential candidate for PARP inhibitors.

In the final PRIMA PRO analysis, results confirmed that niraparib first-line maintenance did not negatively affect HRQOL versus placebo. Disease progression caused sustained HRQOL deterioration across arms, emphasizing the clinical importance of extending progression-free survival to preserve patient HRQOL.

Finally, we summarize current challenges-including limited accessibility, resistance mechanisms, and toxicities-and outline future directions, such as novel biomarkers, liquid biopsy for real-time resistance monitoring, and innovative adaptive trial designs. This review highlights the evolution of DDR-targeted therapy in pancreatic cancer toward personalized, combination-based precision medicine.

This case expands the morphologic spectrum of Stensen's duct carcinoma, underscores the challenges in clinical, radiologic, and pathologic interpretation of masses at this site, and suggests a potential association between homologous recombination deficiency and this translocation-associated malignancy.

P1, N=19, Not yet recruiting, Shanghai Gynecologic Oncology Group

Although PARP inhibitor olaparib has been approved for metastatic CRPC patients bearing BRCA1/2 mutations, its application is confined to this specific patient subpopulation...Their synergistic effect was confirmed in ex vivo explants from human PCa specimens. Our findings demonstrated CDK9 as a master regulator of BRCAness and proposed targeting CDK9 as a potential strategy to sensitize CRPC patients without BRCA1/2 mutations to PARP inhibition.

HRD represents a reliable independent prognostic biomarker in HR+/HER2- breast cancer in this cohort, with an inverse association with TILs suggesting immune evasion. Its potential impact on prognosis and treatment requires further validation in prospective clinical trials.

Screening identified elimusertib (ATR inhibitor), proteasome inhibitors (ixazomib, carfilzomib), and dinaciclib (Cdk1/2/5/9 inhibitor) as synergistic agents with olaparib. These results demonstrate that elimusertib is a very potent ATR inhibitor for combination with olaparib and provide mechanistic insight into this synergy through replication fork interference. Because this synergy spanned both HRD and HRP organoids, these findings support further preclinical optimization and well-designed clinical evaluation of the olaparib-elimusertib combination in HGSC, with attention to dose-finding, hematologic safety, and patient selection.

These data demonstrate that targeting HRD yields promising outcomes in stage III, HER2-negative, HRD breast cancer and that intensified chemotherapy with autologous stem cell rescue does not provide any advantage over state-of-the-art chemotherapy plus olaparib.