Cancer and Metastasis Reviews

, Volume 32, Issue 1–2, pp 147–162 | Cite as

Targeting the Ras–ERK pathway in pancreatic adenocarcinoma

  • Cindy Neuzillet
  • Pascal Hammel
  • Annemilaï Tijeras-Raballand
  • Anne Couvelard
  • Eric Raymond
NON-THEMATIC REVIEW

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.

Keywords

Pancreatic cancer Pancreatic adenocarcinoma MAP kinases Targeted therapies MEK inhibitors ERK EMT Resistance 

Supplementary material

10555_2012_9396_MOESM1_ESM.doc (38 kb)
ESM 1(DOC 38 kb)

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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Cindy Neuzillet
    • 1
    • 2
  • Pascal Hammel
    • 2
  • Annemilaï Tijeras-Raballand
    • 3
  • Anne Couvelard
    • 4
  • Eric Raymond
    • 1
  1. 1.INSERM U728 and Department of Medical OncologyBeaujon University Hospital (AP-HP Paris 7 Diderot)ClichyFrance
  2. 2.Department of Gastroenterology and PancreatologyBeaujon University Hospital (AP-HP Paris 7 Diderot)ClichyFrance
  3. 3.Preclinical DepartmentAAREC Filia ResearchBoulogne-BillancourtFrance
  4. 4.INSERM U773 and Department of PathologyBichat University Hospital (AP-HP Paris 7 Diderot)ParisFrance

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