Rubraca (rucaparib)

In recent years, derivatives of olaparib and rucaparib have been radiolabeled for noninvasive imaging of PARP1 expression and targeted radionuclide therapy of PARP-expressing tumors. Methods for the chiral separation of precursor permitted radiolabeling of [211At]talazoparib without the need for separation from its inactive 211At-labeled enantiomer after radiolabeling, and scaled-up production was optimized. [211At]talazoparib exhibited promising potential as a targeted radiotherapeutic, particularly for settings where locoregional administration is warranted.

PBRM1 loss confers selective hypersensitivity to PARP inhibitors, which intensify DNA-damage signaling, promote G2/M checkpoint arrest, trigger apoptosis, and induce stress-response genes such as CSRNP3. Although this effect appears context-dependent and was not observed uniformly across all PBRM1-/- models tested. These results support further evaluation of PBRM1 as a potential predictive biomarker in defined molecular contexts rather than as a universal marker of PARP inhibitor sensitivity.

HRDetect predicts survival and sensitivity to PARPi in OC. Combined with RS-based clustering, it reveals unappreciated genomic heterogeneity, and supports a nuanced stratification framework to improve precision oncology in OC.

It details the efficacy of major PARPis (olaparib, niraparib, rucaparib, and fuzuloparib) in pivotal trials. Overcoming resistance requires a multipronged approach integrating deep molecular profiling, mechanism-informed combination therapies, and biomarker-driven clinical trial designs. Future progress hinges on translating biological insights into personalized treatment strategies to extend durable remission for a greater portion of patients, while also addressing the economic and ethical implications of long-term maintenance therapy.

Querying the Connectivity Map/LINCS library with the human component of the module highlighted anthracycline-like topoisomerase II poisons (valrubicin, etoposide, amsacrine) and the PARP inhibitor rucaparib among the ~0.2% most negative connectivity scores, while directly targeting TOP2A and/or PARP1. Finally, extracellular-vesicle microRNA (EV-miRNA) profiling in human DLBCL showed that differentially expressed EV-miRNAs, including let-7 family members, miR-21-5p, miR-124-3p and miR-205-5p, converge on the same TOP2A/PARP1-centred core. These cross-species, multi-layer data support topoisomerase II poisons and PARP inhibition as coherent, network-anchored candidate therapies for canine DLBCL, with module scores and EV-miRNAs as candidate biomarkers.

Among PARPi, Talazoparib (Talzenna®) is a potent therapy for patients with locally advanced or metastatic BC (mBC) with germline BRCA mutations (gBRCAm) and HER2-negative status, demonstrating the highest potency (IC50 = 0.57 nM), which is 4-10 times lower than that of other PARP inhibitors; olaparib (2.0 nM), rucaparib (1.9 nM), and veliparib (4.7 nM), indicating superior efficacy. The latest advancements in talazoparib research, including all related clinical trials (Phase 1-3) for the treatment of BC, OC, and other solid tumors (STs), are also summarized. A comprehensive analysis of all clinical trials involving talazoparib, whether as monotherapy or in combination with other drugs, elucidates its potential to improve clinical outcomes, address drug resistance, and explore synergistic combinations with other PARPi or novel agents, thereby providing insights into the clinical utility of talazoparib.

Immune infiltration analysis and drug sensitivity testing (e.g. AG-014699, Axitinib, BX-795, and Cisplatin) were also conducted. IL-6 emerged as a core gene with significant expression difference across cellular and tissue levels. FAO plays a critical role in the prognosis of GC, and IL-6 may serve as a key biomarker for diagnosis and therapeutic strategies.

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.