P2, N=180, Terminated, Gustave Roussy, Cancer Campus, Grand Paris | N=600 --> 180 | Unknown status --> Terminated; study design, change of standard of care, enrollment difficulties

Critically, this process is dependent on the tumor suppressors BRCA1 and BRCA2 and is associated with the BRCA2-dependent accumulation of RAD51 recombinase in chromatin. Our data identify nascent strand gaps that are induced by olaparib independently of replication fork reversal and/or PRIMPOL-mediated repriming and that are repaired by a BRCA2-dependent process that we propose is daughter-strand gap protection and/or repair occurring hundreds of kilobases behind DNA replication forks.

This phase II trial evaluated the efficacy and safety of combining niraparib with the PD-1 inhibitor HX008 in patients with metastatic breast cancer who had germline DNA damage response (DDR) mutations. Somatic TP53 mutations significantly correlated with shorter PFS, while ASXL1 mutations correlated with longer PFS. This chemotherapy-free regimen demonstrates promising efficacy and a tolerable safety profile in patients with metastatic breast cancer and germline DDR mutations, providing a novel therapeutic option for this patient population, even those with brain metastases.

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.

The PARP inhibitor talazoparib (TAL) combined with the alkylating agent temozolomide (TMZ) produces synergistic cytotoxicity selectively in mtp53, but not wild-type p53 (wtp53), breast cancer cells and organoids. These findings reveal a previously unrecognized mechanism by which the mutant p53-PARP axis enables replication stress tolerance and drives cancer metastasis. We show mutation of p53 in TNBC provides an additional biomarker-guided framework to improve PARPi therapeutic outcomes.

In the field of urological malignancies, the approval of olaparib for metastatic castration-resistant prostate cancer with BRCA1/2 mutations has led to the practical application of cancer genomic medicine in many cases. However, various challenges exist in its implementation and clinical utilization. This review outlines cancer genomic medicine in urological malignancies, focusing on the types and characteristics of genetic tests performed in clinical settings, as well as the accessibility of treatments based on their results.

P1, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027

However, the combination of SR-4835 with cisplatin or olaparib primarily exhibited an additive, not synergistic, effect. In summary, the present findings indicate that CDK12/13 inhibitor SR-4835 has potent anti-cancer effects accompanied by a BRCAness induction, but fails to achieve synergistic effects with cisplatin or olaparib in OC cells.

Combined inhibition of LSD1 and PARP1, using SP2509/SP2577 and olaparib, respectively, synergistically hinders NER, induces apoptosis, reduces tumor burden, and prolongs the survival of multiple BAP1-deficient pancancer in vitro models and in vivo xenografts. In conclusion, our results provide a deubiquitination landscape of BAP1; elucidate the mechanisms of action of BAP1, LSD1, and PARP1 in pancancers; and describe a promising combination therapeutic strategy applicable across multiple cancers with BAP1 mutations.

P1, N=52, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Aug 2030 --> Dec 2026

P2, N=87, Not yet recruiting, National Cancer Institute (NCI)