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. 2023 Oct;9(10):780-781.
doi: 10.1016/j.trecan.2023.07.016. Epub 2023 Aug 3.

Targeting TEAD-ious resistance

Connor A Ott  1 , Andrew E Aplin  2
Affiliations

Targeting TEAD-ious resistance

Connor A Ott et al. Trends Cancer. 2023 Oct.

Abstract

Recent advances in targeting mutant KRAS are limited by resistance. A recent study in Nature Cancer by Hagenbeek et al. utilizes a novel inhibitor that targets the TEAD transcription factor, GNE-7883, to overcome resistance to KRAS inhibitors. Thus, TEAD inhibitors may maximize the durability of KRAS inhibitors in patients with cancer.

Keywords: G12C; KRAS; TAZ; TEAD; TEAD inhibitor; YAP; drug tolerance; resistance.

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Conflict of interest statement

Declaration of interests None declared by authors.

Figures

Figure 1.
Figure 1.. Schematic of GNE-7883 functionally reducing adaptive resistance to sotorasib treatment.
A. Sotorasib inhibits the RAS/RAF/MEK/ERK pathway, which decreases cancer cell growth and survival. B. Small populations of cells survive sotorasib treatment, developing resistance and showing elevated levels of YAP/TAZ target gene expression. C. Tumor eventually develops resistance to sotorasib when administered as a monotherapy. However, combination with GNE-7883 inhibits TEAD-driven resistance and results in more effective targeting in mutant KRAS cancer.
See this image and copyright information in PMC

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