HRD (Homologous Recombination Deficiency)

Chemo-immunotherapy with pembrolizumab has become the first to show the ultimate overall survival advantage in the early-stage TNBC (KEYNOTE-522) with 65% pathologic complete response (pCR) and 86.6% 5-year survival, establishing a novel standard-of-care...Mechanistic insights alongside multi-omics, computational, and biologic innovation are making a paradigm shift in TNBC- once historically fatal, a disease that could be controlled and cured. Further development of the predictive biomarkers, equity of access plans and avoidance of immune toxicity will be central to universal implementation of these immunotherapy advances.

P1/2, N=357, Active, not recruiting, AstraZeneca | Trial completion date: Dec 2025 --> Jun 2026

Furthermore, we found hemizygous loss to be a common tumor suppression mechanism among helicases, present in 35% of all cancers. Overall, our enzyme-family approach highlights helicases, including AQR, as key potential cancer drivers.

We further explore how advanced architectures like Vision Transformers (ViTs) and Graph Neural Networks (GNNs) can delineate the tumor microenvironment and predict therapeutic response. Finally, we discuss critical hurdles to clinical translation-such as model generalizability, the need for causal AI, and the data bottleneck-while examining future paradigms like foundation models and patient-specific "digital twins." This review highlights AI's revolutionary potential to link imaging phenotype with molecular genotype, advancing a new era of precision medicine in gynecologic oncology.

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.

Key molecular mechanisms underlying these synergistic effects include modulation of reactive oxygen species production, PARP activation, HR pathway regulation, cell cycle control, and induction of autophagy and apoptosis. Nevertheless, challenges including drug resistance, toxicity, and heterogeneous clinical responses highlight the need for biomarker-driven patient selection, optimized dosing schedules, and a deeper understanding of tumor-specific signaling crosstalk.

This includes combining agents like CDDP (cisplatin) with inhibitors of RAD54, such as J54. These approaches may offer alternatives to androgen deprivation therapy (ADT), which is often ineffective in advanced or treatment-resistant PCa common among AA men. This work underscores the importance of integrating genetic, environmental, and therapeutic insights to address PCa disparities.

P2, N=63, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Trial completion date: Jan 2028 --> Jun 2026 | Trial primary completion date: Jan 2028 --> Sep 2025

P2, N=326, Active, not recruiting, Merck Sharp & Dohme LLC | Trial primary completion date: Jun 2026 --> Aug 2025

Functional validation through RNA interference demonstrated that OAS3 knockdown significantly induced apoptosis in THP-1 cells. This study demonstrates that OAS3 acts as a pivotal modulator in the complex network of cancer progression, highlighting its dual role in both tumorigenesis and immune response regulation.

ERpHER2n HRD tumors show features of aggressive disease, but do not display a distinct transcriptional or DNA methylation profile that clearly differentiates them from HR-proficient tumors. Though numbers are limited, we present early evidence that HRD stratification by WGS could impact therapeutic strategies, as HRD BCs trended to poorer outcomes when not treated with chemotherapy.