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01-06-2013 | NON-THEMATIC REVIEW

Targeting the Ras–ERK pathway in pancreatic adenocarcinoma

Authors: Cindy Neuzillet, Pascal Hammel, Annemilaï Tijeras-Raballand, Anne Couvelard, Eric Raymond

Published in: Cancer and Metastasis Reviews | Issue 1-2/2013

Abstract

Pancreatic ductal adenocarcinoma (PAC) stands as the poorest prognostic tumor of the digestive tract with limited therapeutic options. PAC carcinogenesis is associated with the loss of function of tumor suppressor genes such as INK4A, TP53, BRCA2, and DPC4, and only a few activated oncogenes among which K-RAS mutations are the most prevalent. The K-RAS mutation occurs early in PAC carcinogenesis, driving downstream activation of MEK and ERK1/2 which promote survival, invasion, and migration of cancer cells. In PAC models, inhibition of members of the Ras–ERK pathway blocks cellular proliferation and metastasis development. As oncogenic Ras does not appear to be a suitable drug target, inhibitors targeting downstream kinases including Raf and MEK have been developed and are currently under evaluation in clinical trials. In this review, we describe the role of the Ras–ERK pathway in pancreatic carcinogenesis and as a new therapeutic target for the treatment of PAC.

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Title: Targeting the Ras–ERK pathway in pancreatic adenocarcinoma
Authors: Cindy Neuzillet
Pascal Hammel
Annemilaï Tijeras-Raballand
Anne Couvelard
Eric Raymond
Publication date: 01-06-2013
Publisher: Springer US
Published in: Cancer and Metastasis Reviews / Issue 1-2/2013
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-012-9396-2

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