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Review
. 2020 Apr 13;37(4):543-550.
doi: 10.1016/j.ccell.2020.03.013.

Targeting the MAPK Pathway in KRAS-Driven Tumors

Matthias Drosten  1 , Mariano Barbacid  2
Affiliations
Free article
Review

Targeting the MAPK Pathway in KRAS-Driven Tumors

Matthias Drosten et al. Cancer Cell. .
Free article

Abstract

KRAS mutations occur in a quarter of all of human cancers, yet no selective drug has been approved to treat these tumors. Despite the recent development of drugs that block KRASG12C, the majority of KRAS oncoproteins remain undruggable. Here, we review recent efforts to validate individual components of the mitogen-activated protein kinase (MAPK) pathway as targets to treat KRAS-mutant cancers by comparing genetic information derived from experimental mouse models of KRAS-driven lung and pancreatic tumors with the outcome of selective MAPK inhibitors in clinical trials. We also review the potential of RAF1 as a key target to block KRAS-mutant cancers.

Keywords: KRAS-driven cancer; MAPK pathway; clinical trials; lung adenocarcinoma; pancreatic ductal adenocarcinoma.

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