Background: Poly-ADP-ribosylation, that is, adding ADP-ribose moieties to a protein, is a unique
type of protein post-translational modification that regulates various cellular processes such as DNA repair,
mitosis, transcription, and cell growth. Small-molecule inhibitors of poly-ADP-ribose polymerase 1 (PARP1)
have been developed as anticancer agents because inhibition of PARP enzymes may be a synthetic lethal strategy
for cancers with or BRCA2 mutations. However, there are still questions surrounding PARP inhibitors.
Methods/Results: Data were collected from Pubmed, Medline, through searching of these keywords: “PARP”,
“BRCA”, “Synthetic lethal” and “Tankyrase inhibitors”. We describe the current knowledge of PARP inhibition
and its effects on DNA damage; mechanisms of resistance to PARP inhibitors; the evolution of PARP inhibitors;
and the potential use of PARP5a/b (tankyrases) inhibitors in cancer treatment.
Conclusion: PARP inhibitors are already showing promise as therapeutic tools, especially in the management of
BRCA-mutated breast and ovarian cancers but also in tumors with dysfunctional BRCA genes. Small-molecule
tankyrase inhibitors are important for increasing our understanding of tankyrase biology.