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. 2008 Jun;9(6):614-30.

Targeting the Raf/MEK/ERK pathway with small-molecule inhibitors

James A McCubrey  1 , Michele Milella, Agostino Tafuri, Alberto M Martelli, Paolo Lunghi, Antonio Bonati, Melchiorre Cervello, John T Lee, Linda S Steelman
Affiliations
  • PMID: 18516761

Targeting the Raf/MEK/ERK pathway with small-molecule inhibitors

James A McCubrey et al. Curr Opin Investig Drugs. 2008 Jun.

Abstract

Mutations occur in some cancer cells and result in elevated expression or constitutive activation of various growth factor receptors. The Raf/MEK/ERK pathway is often activated by mutations in these growth factor receptors. This pathway is regulated by upstream Ras, which is mutated in 20 to 30% of human cancers. B-Raf is also activated by mutation, especially in melanoma and thyroid cancers. Many of the events elicited by the Raf/MEK/ERK pathway have direct effects on survival and proliferative pathways. Aberrant regulation of the Raf/MEK/ERK pathway can contribute to uncontrolled cell growth and lead to malignant transformation. The effective targeting of this pathway may result in the suppression of cell growth, and death of malignant cells. This review focuses on targeting the Raf/MEK/ERK pathway with small-molecule inhibitors for the treatment of cancer.

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