Targeting the MAPKRASRAF signaling pathway in cancer therapy

Libero Santarpia, Scott M. Lippman, Adel K. El-Naggar

Research output: Contribution to journalArticlepeer-review


Introduction: The MAPK pathway comprises several key signaling components and phosphorylation events that play a role in tumorigenesis. These activated kinases transmit extracellular signals that regulate cell growth, differentiation, proliferation, apoptosis and migration functions. Alteration of the RASRAFMEKERKMAPK (RASMAPK) pathway has been reported in human cancer as a result of abnormal activation of receptor tyrosine kinases or gain-of-function mutations mainly in the RAS or RAF genes. These pathways are considered potential therapeutic targets for cancer treatment. Recently, several small-molecule inhibitors targeting this pathway have been developed and are currently being tested in clinical trials. Areas covered: The biological role of the RASMAPK pathway, the consequence of its disregulation and the development of small-molecule inhibitors. The rationale for targeting the RASMAPK pathway and the application and the results of various inhibitory molecules as anticancer agents in clinical trials. Expert opinion: Inhibitors of MEK and particularly of RAF kinases have shown effectiveness in clinical trials with manageable side effects. RAS and BRAF genes need to be analyzed for mutations as markers of response to treatments and to avoid paradoxical effects. Further characterization of the RASMAPK molecular mechanisms regulation in malignant cells or underlying the acquired resistance to RAF inhibitors will facilitate development of novel combination therapies.

Original languageEnglish
Pages (from-to)103-119
Number of pages17
JournalExpert Opinion on Therapeutic Targets
Issue number1
Publication statusPublished - Jan 2012


  • Extracellular signal-regulated kinase (ERK)
  • Inhibitors
  • MAP kinase kinase (MEK)
  • Mitogen-activated protein kinase (MAPK)
  • RAF
  • RAS
  • Targeted therapies

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Clinical Biochemistry
  • Molecular Medicine


Dive into the research topics of 'Targeting the MAPKRASRAF signaling pathway in cancer therapy'. Together they form a unique fingerprint.

Cite this