PARP inhibitors in head and neck cancer: Molecular mechanisms, preclinical and clinical data.

Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have revolutionized the treatment landscape in several cancers. PARPi increase DNA damage particularly in tumors with underlying defects in DNA repair. In addition to PARPi-induced DNA damage, PARPi enhance immune priming and induce adaptive upregulation of programmed death ligand 1 (PD-L1) expression. Patients with head and neck squamous cell carcinoma (HNSCC) are characterized by aberrant DNA repair pathways, including nucleotide excision repair (NER), base excision repair (BER) and DNA double-strand breaks (DSBs) repair and these deregulated repair mechanisms are implicated in both the pathogenesis of the disease and the outcome of therapy. Cisplatin represents the cornerstone of treatment of HNSCC and cisplatin resistance impedes successful treatment outcomes. To this end, research strategies that are testing modulation of cisplatin sensitivity by PARPi are of particular interest. Moreover, given the immune modulating effects of PARPi and the recent approval of Programmed Cell Death- 1 (PD-1) checkpoint inhibitors in HNSCC, the design of trials combining PARPi and PD-1 checkpoint inhibitors represent a rational research strategy. In this review, we summarize data supporting the integration of PARP inhibitors into HNSCC therapeutic strategy.