Recent developments in targeting ras downstream effectors for ras-driven cancer therapy

Ozge Tatli, Gizem Dinler Doganay*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

4 Citations (Scopus)

Abstract

Aberrant activity of oncogenic rat sarcoma virus (RAS) protein promotes tumor growth and progression. RAS-driven cancers comprise more than 30% of all human cancers and are refractory to frontline treatment strategies. Since direct targeting of RAS has proven challenging, efforts have been centered on the exploration of inhibitors for RAS downstream effector kinases. Two major RAS downstream signaling pathways, including the Raf/MEK/Erk cascade and the phosphatidylinositol-3-kinase (PI3K) pathway, have become compelling targets for RAS-driven cancer therapy. However, the main drawback in the blockade of a single RAS effector is the multiple levels of crosstalk and compensatory mechanisms between these two pathways that contribute to drug resistance against monotherapies. A growing body of evidence reveals that the sequential or synergistic inhibition of multiple RAS effectors is a more convenient route for the efficacy of cancer therapy. Herein, we revisit the recent developments and discuss the most promising modalities targeting canonical RAS downstream effectors for the treatment of RAS-driven cancers.

Original languageEnglish
Article number7561
JournalMolecules
Volume26
Issue number24
DOIs
Publication statusPublished - 1 Dec 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • PI3K-mTOR
  • Raf/MEK/Erk
  • RAS effectors
  • RAS-driven cancers

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