Mutant RAS and the tumor microenvironment as dual therapeutic targets for advanced colorectal cancer

Jorien B.E. Janssen, Jan Paul Medema, Elske C. Gootjes, Daniele V.F. Tauriello*, Henk M.W. Verheul

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

14 Citations (Scopus)

Abstract

RAS genes are the most frequently mutated oncogenes in cancer. These mutations occur in roughly half of the patients with colorectal cancer (CRC). RAS mutant tumors are resistant to therapy with anti-EGFR monoclonal antibodies. Therefore, patients with RAS mutant CRC currently have few effective therapy options. RAS mutations lead to constitutively active RAS GTPases, involved in multiple downstream signaling pathways. These alterations are associated with a tumor microenvironment (TME) that drives immune evasion and disease progression by mechanisms that remain incompletely understood. In this review, we focus on the available evidence in the literature explaining the potential effects of RAS mutations on the CRC microenvironment. Ongoing efforts to influence the TME by targeting mutant RAS and thereby sensitizing these tumors to immunotherapy will be discussed as well.

Original languageEnglish
Article number102433
JournalCancer Treatment Reviews
Volume109
DOIs
Publication statusPublished - Sept 2022
Externally publishedYes

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