Emerging Raf inhibitors

James A. McCubrey, Linda S. Steelman, Steven L. Abrams, William H. Chappell, Suzanne Russo, Roger Ove, Michele Milella, Agostino Tafuri, Paolo Lunghi, Antonio Bonati, Franca Stivala, Ferdinando Nicoletti, Massimo Libra, Alberto M. Martelli, Giuseppe Montalto, Melchiorre Cervello

Research output: Contribution to journalArticlepeer-review


Background: The Raf/MAPK kinase/extracellular-signal-regulated kinase pathway is often activated by genetic alterations in upstream signaling molecules. An integral component of this pathway, BRAF, is also activated by mutation, especially in melanoma and thyroid cancers. The Raf/MAPK kinase/extracellular-signal-regulated kinase pathway has profound effects on proliferative, apoptotic and differentiation pathways as well as the sensitivity and resistance to chemotherapeutic drugs. Objectives/methods: This review discusses targeting of Raf which could control abnormal proliferation in cancer and other proliferative diseases. The important roles that genetics plays in the response of patients to Raf inhibitors is also evaluated. We also discuss the rationales for approaches combining Raf inhibitors and chemotherapeutic drugs. Results/conclusions: Various Raf inhibitors have been developed and are being clinically used to treat patients with melanoma, thyroid, hepatocellular and renal cell cancers. Some 'Raf-kinase inhibitors' affect other kinases which are also expressed on malignant cells; yet, these inhibitors have proven useful in the therapy of certain cancer patients. Other more recently developed Raf specific inhibitors have shown success in the treatment of tumors bearing Raf mutations. The development of Raf inhibitors has significantly advanced cancer therapy in the past decade.

Original languageEnglish
Pages (from-to)633-648
Number of pages16
JournalExpert Opinion on Emerging Drugs
Issue number4
Publication statusPublished - Dec 2009


  • Apoptosis
  • Cancer
  • ERK
  • Kinases
  • MEK
  • Proliferative disorders
  • Protein phosphorylation
  • Raf
  • Raf inhibitors
  • Signal transduction

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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