Poly (ADP-ribose) polymerase (PARP) inhibitors approved for the treatment of cancer.
Level 5 - mechanism / opinion, no new human data
Narrative review of drug mechanisms and regulatory approvals without original clinical trial data or systematic synthesis.
PubMed 41349848 · doi:10.1016/j.phrs.2025.108058
What was done
This narrative review summarizes the biological role of the human PARP enzyme family (specifically PARP1/2/3 in DNA damage repair), the rationale for targeting homologous recombination repair-deficient cancers (including BRCA1/2 mutations), and the current global regulatory approvals for clinical PARP inhibitors.
What was found
Cells experience an estimated 10,000 to 100,000 single-strand breaks and base lesions per day requiring PARP-mediated repair. The US FDA has approved four oral PARP inhibitors (olaparib, rucaparib, niraparib, and talazoparib) across ovarian, breast, prostate, and pancreatic cancers with homologous recombination repair deficiencies, utilized in neoadjuvant, adjuvant, and maintenance settings. China's NMPA has approved three additional agents (fuzuloparib, pamiparib, and senaparib) for ovarian cancer. All seven agents comply with Lipinski's rule of five. However, acquired drug resistance emerges in most treated patients within 1 to 2 years.
Why it matters
PARP inhibitors represent a major class of targeted therapies exploiting synthetic lethality in DNA repair-deficient tumors across multiple solid tumor types, though secondary resistance remains a primary clinical hurdle.
Limits
The abstract provides a broad narrative summary rather than a systematic review or meta-analysis. It does not report comparative efficacy statistics (such as progression-free or overall survival), specific safety and toxicity profiles, or quantitative response rates across individual tumor types.
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