Immunomodulatory roles of PARPs: Shaping the tumor microenvironment, one ADP-ribose at a time

Curr Opin Chem Biol. 2023 Oct 4;77:102402. doi: 10.1016/j.cbpa.2023.102402. Online ahead of print.ABSTRACTPARPs encompass a small yet pervasive group of 17 enzymes that catalyze a post-translational modification known as ADP-ribosylation. PARP1, the founding member, has received considerable focus; however, in recent years, the spotlight has shifted to other members within the PARP family. In this opinion piece, we first discuss surprising findings that some FDA-approved PARP1 inhibitors activate innate immune signaling in cancer cells that harbor mutations in the DNA repair pathway. We then discuss hot-off-the-press genetic and pharmacological studies that reveal roles for PARP7, PARP11, and PARP14 in immune signaling in both tumor cells and tumor-associated immune cells. We conclude with thoughts on tuning PARP1-inhibitor-mediated innate immune activation and explore the unrealized potential for small molecule modulators of other PARP family members as next-generation immuno-oncology drugs.PMID:37801755 | DOI:10.1016/j.cbpa.2023.102402
Source: Current Opinion in Chemical Biology - Category: Biochemistry Authors: Source Type: research