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 Printable version |
Targeting the Ras-MAP kinases pathway to treat pancreatic adenocarcinoma |
Hépato-Gastro. Volume 19, Number 3, 152-61, Mars 2012, Mini-revue
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 Résumé
Texte intégral
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Author(s) : Cindy Neuzillet, Pascal Hammel |
Summary : Pancreatic ductal adenocarcinoma (PAC) has the worst prognosis among all the digestive cancers. Therapeutic options for advanced PAC are limited. New molecules are strongly needed. The Ras-Raf-MEK-ERK signaling pathway is one of the best characterized in cancer biology. It is initiated by growth factors and regulates the expression of various genes involved in cell cycle regulation, proliferation, survival, migration, angiogenesis and differentiation. It is aberrantly activated in many cancers, including PAC, which displays the highest incidence of K-Ras mutations (70%-90%). Inhibitors of this signaling pathway have been developed. Among them, MEK inhibitors are to date the most advanced in clinical therapeutic studies for PAC. In this review, we will describe the role of the Ras-Raf-MEK-ERK pathway in PAC tumorigenesis and as a new therapeutic target. In addition, we aim to highlight the limits of such a strategy and the role of combined treatments. |
Keywords : pancreatic cancer, pancreatic adenocarcinoma, MAP kinases, targeted therapies, MEK inhibitors, AP, adénocarcinome du pancréas, SG, survie globale, HR,
hazard ratio, GEF,
guanine nucleotide exchange factors, GAP,
GTPase-activating proteins, MEK,
mitogen-activated extracellular signal regulated kinase, ERK,
extracellular signal-regulated kinase, TEM, transition épithélio-mésenchymateuse, PanIN,
pancreatic intraepithelial neoplasia, proliférations intra-épithéliales pancréatiques, SSP, survie sans progression, MEK-i, inhibiteurs de MEK, RECIST,
response evaluation criteria in solid tumors, GIST,
gastro-intestinal stromal tumor, tumeur stromale gastro-intestinale |
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