[Focus on targeting the Ras-MAPK pathway: the Mek inhibitors].

Abstract

The Ras/Raf/Mek/Erk pathway is a key component of tumor progression and modulates proliferation, survival, differentiation and angiogenesis. Hyperactivation of this pathway is highly implicated in tumorigenesis especially by gain of function mutation of Kras or Braf. Mek position at the end of the pathway seems to be a promising new therapeutic target in the Kras or Braf mutated cancers. In this review, we aimed at describing the Ras/Raf/Mek/Erk pathway, the new therapeutic approaches in solid tumors and their toxicities. However, there seems to be predictives factors of tumor responses to these new agents and mechanisms of resistance that we will tend to analyse.

• Authors: Capucine Baldini, Boris Duchemann, Antoine Hollebecque, Émilie Routier, Andreea Varga, Anas Gazzah, Rastio Bahleda, Benjamin Besse, Jean-Charles Soria, Christophe Massard
• Journal: Bulletin du cancer (Bull Cancer) Vol. 99 Issue 9 Pg. 865-74 (Sep 2012) ISSN: 1769-6917 [Electronic] France
• Vernacular Title: Mise au point sur l'inhibition de la voie Ras-MAPK: les inhibiteurs de Mekl.
• PMID: 25471668 (Publication Type: English Abstract, Journal Article, Review)

Chemical References

• Antineoplastic Agents
• Neoplasm Proteins
• Protein Kinase Inhibitors
• BRAF protein, human
• Proto-Oncogene Proteins B-raf
• Extracellular Signal-Regulated MAP Kinases
• Mitogen-Activated Protein Kinase Kinases
• ras Proteins

Topics

• Antineoplastic Agents (adverse effects, pharmacology)
• Breast Neoplasms (drug therapy, metabolism)
• Carcinoma, Non-Small-Cell Lung (drug therapy, metabolism)
• Clinical Trials as Topic
• Colorectal Neoplasms (drug therapy, metabolism)
• Diarrhea (chemically induced)
• Drug Eruptions (etiology)
• Drug Resistance, Viral
• Extracellular Signal-Regulated MAP Kinases (physiology)
• Eye Diseases (chemically induced)
• Female
• Humans
• Lung Neoplasms (drug therapy, metabolism)
• MAP Kinase Signaling System (drug effects)
• Melanoma (drug therapy, metabolism)
• Mitogen-Activated Protein Kinase Kinases (antagonists & inhibitors, metabolism)
• Neoplasm Proteins (antagonists & inhibitors, metabolism)
• Neoplasms (drug therapy)
• Protein Kinase Inhibitors (adverse effects, pharmacology)
• Proto-Oncogene Proteins B-raf (antagonists & inhibitors, metabolism)
• ras Proteins (antagonists & inhibitors, metabolism)