Related Experiment Video

Updated: Jul 1, 2025

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
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Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

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Targeting the EGFR/RAS/RAF signaling pathway in anticancer research: a recent update on inhibitor design and clinical

Rima Hajjo1,2,3, Dima A Sabbah1, Sanaa K Bardaweel4

  • 1Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan.

Expert Opinion on Therapeutic Patents
|March 7, 2024
PubMed
Abstract

Insights

This review covers new EGFR, KRAS, and BRAF inhibitors developed between 2020-2023. Strategies like PROTACs and novel inhibitors aim to overcome drug resistance and reduce toxicity in cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The EGFR/RAS/RAF signaling pathway is crucial for cell growth and proliferation.
  • Protein-protein interactions within this pathway provide targets for drug discovery.
  • Significant advancements in targeting this pathway have been made in recent years.

Purpose of the Study:

  • To review drug design and development of inhibitors targeting EGFR, RAS, and RAF proteins.
  • To detail structures, selectivity, efficacy, and combination therapies of these inhibitors over the past 3 years.
  • To explore strategies for overcoming drug resistance and minimizing toxicities.

Main Methods:

  • Review of clinical trials and patents concerning EGFR, KRAS, and BRAF inhibitors from 2020 to 2023.
  • Analysis of advancements in the design and synthesis of Proteolysis Targeting Chimeras (PROTACs).

Main Results:

  • Development of novel inhibitors targeting EGFR, KRAS, and BRAF.
  • Exploration of combination therapies and PROTACs for enhanced efficacy.
  • Strategies identified to combat drug resistance and reduce treatment-related toxicities.

Conclusions:

  • Allosteric fourth-generation EGFR inhibitors are vital for overcoming resistance.
  • Covalent, allosteric, and combination therapies, along with PROTAC degraders, are key for KRAS and BRAF inhibitors.
  • Future research directions focus on improved resistance management and toxicity profiles.
Keywords:
BRAFEGFRKRASPROTACsanticancercombination therapycovalent drugsresistance

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