Sonu Kumar
Department of Pharmacy Practice, ISF College of Pharmacy, Moga, India
Publications
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Research Article
Synthetic Lethality in Cancer: Mechanistic and Therapeutic Insights into PARP Inhibitors, BRCA Mutations and Homologous Recombination Deficiency (HRD)
Author(s): Sonu Kumar*
Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) represent a paradigm shift in precision oncology, exploiting synthetic lethality to selectively target tumor cells deficient in homologous recombination repair (HRR) pathways, particularly those harboring BRCA1/2 mutations [1]. PARP enzymes, primarily PARP1 and PARP2, are central to the repair of single-strand DNA breaks through the base excision repair pathway. Pharmacologic inhibition of PARP leads to persistent DNA damage accumulation, replication fork collapse, and lethal double-strand breaks in HRR- defective cells [2,3]. Loss-of-function mutations in BRCA1, BRCA2, or other HRR genes (e.g., ATM, PALB2, RAD51) define a homologous recombination– deficient (HRD) phenotype that confers enhanced susceptibility to PARPi-induced cytotoxicity [4]. The clinical efficacy of PARPi—including olaparib, niraparib, rucaparib, and.. Read More»