Rubraca (rucaparib)

The senescence-like phenotype, HIF1α activation and lactate production were attenuated in tumor xenografts co-treated with PARP inhibitor Rucaparib and mitochondrial antioxidant. The metabolic reliance on mtROS-driven glycolysis in ovarian cancer cells treated with PARP inhibitors has implications in cancer treatment.

This study identifies eight EMT-related prognostic genes in PTC and highlights their potential value as biomarkers for prognostic evaluation and therapeutic stratification.

Four PARP inhibitors, olaparib, niraparib, rucaparib, are approved by the Food and Drug Administration (FDA) approved. Despite these advances, selective inhibitors for ARTs remain underexplored. Ongoing research focuses on overcoming PARP inhibitor resistance, improving biomarker-driven patient selection, and expanding therapeutic strategies that target ART-related pathways.

These collective findings suggest the potential of immunotherapy for CRPC in overcoming resistance barriers and improving patient outcomes, with bispecific T cell engagers (Xaluritamig, 59% PSA50) and PSMA-directed CAR-T therapy (P-PSMA-101, >50% PSA reduction) emerging as the most promising near-term candidates and biomarker-stratified combinations (nivolumab plus rucaparib, 84.6% PSA50, in HRR-deficient patients) illustrating the transformative power of precision patient selection; however, these findings require validation in larger, biomarker-stratified trials before definitive conclusions can be drawn. Translating this potential into clinical reality requires optimized patient selection through predictive biomarkers and rigorously validated Phase III trials to confirm durable clinical responses and long-term survival benefits.

hMOB2 depletion sensitized A549 cells to olaparib and rucaparib, resulting in a marked reduction in long-term clonogenic survival. Sensitization required functional p53, as it was absent in p53-null cells but restored upon p53 re-expression. These findings suggest that hMOB2 contributes to PARP inhibitor responses in lung cancer cells and underscore the complexity of PARP inhibitor sensitivity beyond classical HR deficiency.

P2, N=79, Completed, University of Colorado, Denver | Active, not recruiting --> Completed | Trial completion date: Dec 2026 --> Feb 2026

P2, N=30, Completed, Medical College of Wisconsin | Active, not recruiting --> Completed

Collectively, VEGF-, PARP-, and FRα-targeted therapies have enabled more rational treatment sequencing, informed combination strategies, and personalized clinical decision-making in ovarian cancer. Ongoing efforts to define optimal sequencing, overcome acquired resistance, and refine predictive biomarkers are expected to further enhance the durability and breadth of benefit from targeted therapies and advance precision oncology in gynecologic malignancies.

P2, N=79, Active, not recruiting, University of Colorado, Denver | Trial completion date: Dec 2025 --> Dec 2026

P1/2, N=25, Terminated, University of Michigan Rogel Cancer Center | Trial completion date: Jun 2028 --> May 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2025 --> May 2025; Due to financial hardships suffered by the stakeholder

P3, N=61, Active, not recruiting, Alliance for Clinical Trials in Oncology | Trial primary completion date: Mar 2026 --> Mar 2027

To enable organelle-specific modulation of PARP activity, we synthesized a series of trialkyl(aryl)phosphonium conjugates of olaparib and rucaparib designed to target mitochondria by cardiolipin binding. Phosphonium conjugation preserves PARP1 inhibitory activity while conferring mitochondrial targeting and enhanced anticancer potency. These findings support the development of mitochondria-targeted PARP inhibitors as a next-generation therapeutic strategy with the potential to improve efficacy and overcome resistance in HR-deficient tumors.