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

Curr Opin Chem Biol. 2023 Dec:77:102402. doi: 10.1016/j.cbpa.2023.102402.

Deja M Brooks ¹, Sudarshan Anand ², Michael S Cohen ³

Affiliations

1 Department of Chemical Physiology and Biochemistry, Oregon Health & Science University, Portland, OR 97239, USA; Program in Molecular and Cellular Biology, Oregon Health & Science University, Portland, OR 97239, USA; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
2 Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Department of Cellular and Developmental Biology, Oregon Health & Science University, Portland, OR 97239, USA.
3 Department of Chemical Physiology and Biochemistry, Oregon Health & Science University, Portland, OR 97239, USA; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA. Electronic address: [email protected].

PMID: 37801755 DOI: 10.1016/j.cbpa.2023.102402

Abstract

PARPs 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.

Name
Email *

	Sorry, but the email address you supplied was invalid.