Poly(ADP-Ribose) Polymerase Inhibition as a Promising Approach for Hepatocellular Carcinoma Therapy.

Abstract

Simple SummaryLiver cancer has very high incidence and mortality rates, making it a major public health problem. Indeed, the available treatments are not numerous, and few strategies exist for patients with advanced cancers. Thus, there is an urgent need to search for new treatment targets. This review provides an overview of one potential target, poly(ADP)ribose polymerase 1, a protein involved in DNA repair pathways and its expression profiles in liver cancer. Inhibition of this protein could potentiate the effects of current treatments and improve therapeutic outcomes for patients.Primary liver cancer is the sixth most common cancer in men and seventh in women, with hepatocellular carcinoma (HCC) being the most common form (75–85% of primary liver cancer cases) and the most frequent etiology being viral infections (HBV and HCV). In 2020, mortality represented 92% of the incidence—830,180 deaths for 905,677 new cases. Few treatment options exist for advanced or terminal-stage HCC, which will receive systemic therapy or palliative care. Although radiotherapy is used in the treatment of many cancers, it is currently not the treatment of choice for HCC, except in the palliative setting. However, as radiosensitizing drugs, such as inhibitors of DNA repair enzymes, could potentiate the effects of RT in HCC by exploiting the modulation of DNA repair processes found in this tumour type, RT and such drugs could provide a treatment option for HCC. In this review, we provide an overview of PARP1 involvement in DNA damage repair pathway and discuss its potential implication in HCC. In addition, the use of PARP inhibitors and PARP decoys is described for the treatment of HCC and, in particular, in HBV-related HCC.