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RAS Function in cancer cells: translating membrane biology and biochemistry into new therapeutics

Walaa E Kattan1,2, John F Hancock1,2

  • 1Department of Integrative Biology and Pharmacology, McGovern Medical School University of Texas Health Science Center at Houston, Houston, TX 77030, U.S.A.

The Biochemical Journal
|August 16, 2020
PubMed

Insights

Targeting mutated RAS proteins in cancer has been challenging. Recent advances focus on inhibiting KRAS, the most common cancer-related RAS isoform, particularly its interactions with the plasma membrane.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The three human RAS proteins are frequently mutated and activated in approximately 20% of human cancers.
  • Constitutive activation of RAS proteins drives uncontrolled cell growth and proliferation, contributing to tumorigenesis.
  • Despite extensive efforts over three decades, inhibiting RAS proteins has proven difficult.

Purpose of the Study:

  • To review recent advancements in the inhibition of KRAS, the most prevalent mutated RAS isoform.
  • To discuss the underlying biological mechanisms of these new inhibition strategies.
  • To highlight the critical role of KRAS-plasma membrane interactions in RAS signaling and therapeutic targeting.

Main Methods:

  • Literature review of recent studies on KRAS inhibition.
  • Analysis of biological pathways involving RAS proteins.
  • Focus on methodologies targeting KRAS-plasma membrane interactions.

Main Results:

  • Emergence of novel therapeutic strategies specifically targeting KRAS.
  • Identification of KRAS-plasma membrane interactions as a key vulnerability.
  • Progress in developing inhibitors for the most mutated RAS isoform.

Conclusions:

  • Recent breakthroughs offer new hope for targeting KRAS-driven cancers.
  • Understanding KRAS-plasma membrane interactions is crucial for developing effective therapies.
  • Targeting KRAS represents a significant step forward in cancer treatment.
Keywords:
RAScancerphospholipidsplasma membranesmall molecule inhibitorstherapeutics

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