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Recent Developments in Targeting RAS Downstream Effectors for RAS-Driven Cancer Therapy

Ozge Tatli1,2, Gizem Dinler Doganay1,3

  • 1Department of Molecular Biology, Genetics-Biotechnology, Graduate School, Istanbul Technical University, Istanbul 34469, Turkey.

Molecules (Basel, Switzerland)
|December 24, 2021
PubMed

Insights

Targeting oncogenic Rat Sarcoma virus (RAS) protein pathways is crucial for treating RAS-driven cancers. Combining inhibitors of multiple RAS effectors offers a promising strategy to overcome drug resistance and improve therapeutic efficacy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Aberrant Rat Sarcoma virus (RAS) protein activity drives tumor growth in over 30% of human cancers.
  • RAS-driven cancers are often resistant to standard treatments, necessitating novel therapeutic strategies.

Purpose of the Study:

  • To review recent advancements in targeting RAS downstream effectors for cancer therapy.
  • To discuss promising therapeutic modalities for RAS-driven malignancies.

Main Methods:

  • Review of scientific literature on RAS signaling pathways and targeted therapies.
  • Analysis of crosstalk and compensatory mechanisms between Raf/MEK/Erk and PI3K pathways.
  • Evaluation of monotherapy versus combination therapy approaches.

Main Results:

  • Directly targeting RAS is challenging, leading to focus on downstream effectors like Raf/MEK/Erk and PI3K pathways.
  • Monotherapies targeting single RAS effectors face drug resistance due to pathway crosstalk.
  • Sequential or synergistic inhibition of multiple RAS effectors shows potential for enhanced efficacy.

Conclusions:

  • Targeting multiple RAS downstream effectors is a more effective strategy than monotherapy for RAS-driven cancers.
  • Combination therapies hold promise for overcoming resistance and improving treatment outcomes.
  • Further research into novel modalities targeting canonical RAS downstream effectors is warranted.
Keywords:
PI3K-mTORRAS effectorsRAS-driven cancersRaf/MEK/Erk

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