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Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
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Biology, pathology, and therapeutic targeting of RAS

J Matthew Rhett1, Imran Khan1, John P O'Bryan1

  • 1Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, United States; Ralph H. Johnson VA Medical Center, Charleston, SC, United States.

Advances in Cancer Research
|July 30, 2020
PubMed

Insights

RAS (Rat-Sarcoma viral oncogene homolog) proteins are key drivers in nearly 30% of human cancers. Despite decades of research, directly inhibiting RAS remains challenging, but new therapies offer hope.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • RAS proteins, identified as human oncogenes, are frequently mutated in human cancers.
  • RAS signaling is crucial for tumor development and maintenance.
  • Directly inhibiting RAS has been a long-standing challenge in cancer therapy.

Purpose of the Study:

  • To detail RAS biology and its role in cell signaling.
  • To elucidate the challenges in developing therapeutic RAS inhibitors.
  • To review past and current efforts in developing RAS-targeted drugs.

Main Methods:

  • Review of existing literature on RAS biology and signaling pathways.
  • Analysis of structural and biochemical properties of RAS proteins.
  • Discussion of historical and contemporary strategies for RAS inhibition.

Main Results:

  • RAS mutations are prevalent in approximately 30% of all human cancers.
  • The central role of RAS in growth factor signaling contributes to its oncogenic potential.
  • Unique structural and biochemical features of RAS present significant therapeutic hurdles.

Conclusions:

  • Despite difficulties, recent advancements have led to promising new drugs entering clinical trials.
  • Understanding RAS biology is critical for overcoming therapeutic challenges.
  • Continued research into RAS inhibitors offers a hopeful outlook for cancer treatment.
Keywords:
AutophagyCancerGTPaseGrowth factor signalingMAPKMonobodyRASSmall molecule inhibitor

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