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Targeting the MAPK Pathway in RAS Mutant Cancers

Sarah G Hymowitz1, Shiva Malek2

  • 1Department of Structural Biology, Genentech Inc., South San Francisco, California 94080.

Cold Spring Harbor Perspectives in Medicine
|February 15, 2018
PubMed

Insights

Targeting KRAS mutant cancers remains challenging. This review explores inhibiting mitogen-activated protein kinase (MAPK) signaling with specific kinase inhibitors to treat these tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • KRAS mutant cancers lack targeted therapies despite extensive drug discovery.
  • Mitogen-activated protein kinase (MAPK) signaling is crucial in KRAS-driven tumorigenesis.

Purpose of the Study:

  • To review challenges and opportunities in targeting KRAS mutant tumors.
  • To explore the use of conformation-specific kinase inhibitors targeting MAPK signaling.

Main Methods:

  • Structural analysis of BRAF and MEK inhibitors.
  • Mechanistic studies of MAPK signaling components.
  • Investigating kinase-dependent and -independent functions.

Main Results:

  • Insights into how MAPK signaling regulates KRAS-driven tumorigenesis.
  • Understanding the role of kinase and non-kinase functions in tumor growth.
  • Identifying strategies for small molecule kinase inhibitor development.

Conclusions:

  • Targeting MAPK signaling offers a promising therapeutic strategy for KRAS mutant cancers.
  • Conformation-specific kinase inhibitors show potential for treating RAS mutant tumors.
  • Further research into MAPK signaling pathways can lead to novel cancer treatments.

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