Targeting the mitogen-activated protein kinase pathway: Physiological feedback and drug response

Christine A. Pratilas, David B. Solit

Research output: Contribution to journalReview articlepeer-review

133 Scopus citations


Mitogen-activated protein kinase (MAPK) pathway activation is a frequent event in human cancer and is often the result of activating mutations in the BRAF and RAS oncogenes. Targeted inhibitors of BRAF and its downstream effectors are in various stages of preclinical and clinical development. These agents offer the possibility of greater efficacy and less toxicity than current therapies for tumors driven by oncogenic mutations in the MAPK pathway. Early clinical results with the BRAF-selective inhibitor PLX4032 suggest that this strategy will prove successful in a select group of patients whose tumors are driven by V600E BRAF. Relief of physiologic feedback upon pathway inhibition may, however, attenuate drug response and contribute to the development of acquired resistance. An improved understanding of the adaptive response of cancer cells to MAPK pathway inhibition may thus aid in the identification of those patients most likely to respond to targeted pathway inhibitors and provide a rational basis for tailored combination strategies.

Original languageEnglish (US)
Pages (from-to)3329-3334
Number of pages6
JournalClinical Cancer Research
Issue number13
StatePublished - Jul 1 2010
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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