Anticipating resistance to KRAS inhibition: a novel role for USP21 in macropinocytosis regulation

Document Type

Article

Publication Date

10-1-2021

Publication Title

Genes & development

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Virtually all PDAC harbors an oncogenic mutation in the KRAS gene, making it the prime target for therapy. Most previous attempts to inhibit KRAS directly have been disappointing, but recent success in targeting some KRAS mutants presages a new era in PDAC therapy. Models of PDAC have predicted that identifying KRAS inhibitor resistance mechanisms will be critical. In this issue of Genes & Development, Hou and colleagues (pp. 1327-1332) identify one such mechanism in which the deubiquitinase USP21 up-regulates the nutrient-scavenging process of macropinocytosis, rescuing PDAC cells from Kras extinction.

PubMed ID

34599002

Volume

35

Issue

19-20

First Page

1325

Last Page

1326

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