Medicine and Health

Targeting USP2 regulation of VPRBP-mediated degradation of p53 and PD-L1 for cancer therapy

J. Yi, O. Tavana, et al.

Exciting discoveries in cancer therapy show that targeting the USP2-VPRBP axis can effectively reactivate p53 and reduce toxicity compared to traditional Mdm2 inhibitors. This innovative approach, explored by authors Jingjie Yi, Omid Tavana, Huan Li, Donglai Wang, Richard J. Baer, and Wei Gu, demonstrates complete tumor regression in wild-type p53 tumors with the combination of a USP2 inhibitor and anti-PD1 antibody.

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Abstract

Mdm2 inhibitors, while effective in reactivating p53 in pre-clinical models, show serious toxicity in clinical trials. This study identifies the USP2-VPRBP axis as a crucial regulator of p53 and PD-L1. VPRBP, a p53 repressor, is stabilized by USP2. The combination of a USP2 inhibitor and anti-PD1 antibody leads to complete tumor regression in wild-type p53 tumors, without the toxicity observed with Mdm2 inhibitors. This USP2/VPRBP targeting strategy offers a promising p53-based cancer therapy.

Publisher

Nature Communications

Published On

Apr 06, 2023

Authors

Jingjie Yi, Omid Tavana, Huan Li, Donglai Wang, Richard J. Baer, Wei Gu

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