PARP inhibitors have transformed treatment of BRCA1/2 -mutated breast cancer but remain limited by acquired resistance, restricted activity in homologous recombination–proficient tumors, and PARP2-related toxicity. This review examines two advances redefining the class: next-generation PARP1-selective inhibitors with improved therapeutic indices, and rational combinations with DNA-repair, epigenetic, immune, endocrine, and antibody-drug conjugate partners. Together, these strategies mark a shift from monotherapy toward mechanism-based combinations that broaden benefit across breast cancer subtypes.
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Reddy et al. (2026) studied this question.
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