PARP mediated DNA damage response, genomic stability and immune responses.

ABSTRACT

Poly(ADP-ribose) polymerase (PARP) enzymes, especially PARP1, play important roles in the DNA damage response and in the maintenance of genome stability, which makes PARPis a classic synthetic lethal therapy for BRCA-deficient tumors. Conventional mechanisms suggest that PARPis exert their effects via catalytic inhibition and PARP-DNA trapping. Recently, PARP1 has been found to play a role in the immune modulation of tumors. The blockade of PARP1 is able to induce innate immunity through a series of molecular mechanisms, thus allowing the prediction of the feasibility of PARPis combined with immune agents in the treatment of tumors. PARPis combined with immunomodulators may have a stronger tumor suppressive effect on inhibiting tumor growth and blocking immune escape.