Role of Poly (ADP-Ribose) Polymerase-1 (PARP1) and Its Inhibitors for Cancer Therapy.

INTRODUCTION

Poly (ADP-ribose) polymerase (PARP) regulates transcription, replication, DNA repair, and the cell cycle. This study examines the multiple functions of PARP beyond DNA repair, including its role in immunological modulation, chemokine signaling, and the regulation of gene expression, particularly during angiogenesis and the epithelial-to-mesenchymal transition.

METHODS

PARP inhibitors are approved for treating malignancies by targeting vulnerabilities associated with homologous recombination (HR) insufficiency, such as that caused by BRCA1/2 malfunction. By contrasting the "double-strand break (DSB)" and "single-stranded DNA (ssDNA) gap" models of synthetic lethality, PARP inhibitors are used to treat BRCA1/2-deficient cancers. We examine how ssDNA gaps and DNA polymerase theta (POLθ) interact to influence treatment outcomes.

RESULTS

This review highlights that advanced research is required to bridge the gap between laboratory models and real-world scenarios, focusing on the therapeutic implications of PARP1 efficacy and resistance mechanisms in BRCA-mutated cancers.

DISCUSSION: PARP inhibitors extend beyond DNA repair, with ssDNA gap-driven lethality and POLθ- mediated resistance shaping efficacy, clinical translation, and emerging roles in metastasis prevention.

CONCLUSION

With an emphasis on specific metastatic sites and PARP-selective inhibitors, we conclude by highlighting recent clinical developments in PARP inhibitors for the prevention and treatment of distant metastases. Because of their promising results in preventing metastatic cancer, PARP inhibitors may be used more frequently in the early stages of cancer.