TY - JOUR
T1 - Immunomodulatory roles of PARPs
T2 - Shaping the tumor microenvironment, one ADP-ribose at a time
AU - Brooks, Deja M.
AU - Anand, Sudarshan
AU - Cohen, Michael S.
N1 - Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cbpa.2023.102402
DO - 10.1016/j.cbpa.2023.102402
M3 - Review article
C2 - 37801755
AN - SCOPUS:85173047404
SN - 1367-5931
VL - 77
JO - Current Opinion in Chemical Biology
JF - Current Opinion in Chemical Biology
M1 - 102402
ER -