PARP1: A comprehensive review of its mechanisms, therapeutic implications and emerging cancer treatments
Carlota J.F. Conceição, Elin Moe, Paulo A. Ribeiro, Maria Raposo
Abstract
The Poly (ADP-ribose) polymerase-1 (PARP1) enzyme is involved in several signalling pathways related to homologous repair (HR), base excision repair (BER), and non-homologous end joining (NHEJ). Studies demonstrated that the deregulation of PARP1 function and control mechanisms can lead to cancer emergence. On the other side, PARP1 can be a therapeutic target to maximize cancer treatment. This is done by molecules that can modulate radiation effects, such as DNA repair inhibitors (PARPi). With this approach, tumour cell viability can be undermined by targeting DNA repair mechanisms. Thus, treatment using PARPi represents a new era for cancer therapy, and even new horizons can be attained by coupling these molecules with a nano-delivery system. For this, drug delivery systems such as liposomes encompass all the required features due to its excellent biocompatibility, biodegradability, and low toxicity. This review presents a comprehensive overview of PARP1 biological features and mechanisms, its role in cancer development, therapeutic implications, and emerging cancer treatments by PARPi-mediated therapies. Although there are a vast number of studies regarding PARP1 biological function, some PARP1 mechanisms are not clear yet, and full-length PARP1 structure is missing. Nevertheless, literature reports demonstrate already the high usefulness and vast possibilities offered by combined PARPi cancer therapy.