RAF signaling in neuroendocrine neoplasms: From bench to bedside

Nicola Fazio, Omar Abdel-Rahman, Francesca Spada, Salvatore Galdy, Sara De Dosso, Jaume Capdevila, Aldo Scarpa

Research output: Contribution to journalArticlepeer-review

Abstract

Neuroendocrine neoplasms are a low-incidence and heterogeneous group of malignancies. In the advanced stage, several therapeutic options can be discussed, including molecular-targeted agents, but biological predicting factors are lacking. A number of molecular targets have been studied over the last decade leading to several phase II studies; however, very few agents progressed to phase III clinical trials. The RAF family of proteins belongs to the mitogen-activated protein kinase (MAPK) pathway, that has a role in several types of cancers, particularly related to BRAF mutations. Indeed BRAF inhibitors have been reported as being effective, mainly in melanoma. However, in neuroendocrine neoplasms BRAF mutations are extremely rare and RAF-1 activation has been reported to inhibit tumor growth in a pre-clinical setting. Therefore, in this field, RAF-1 activators rather than BRAF inhibitors should be clinically investigated. This article reviews the basic science as well as clinical data of RAF signaling in advanced neuroendocrine neoplasms with special emphasis on the potential role of both RAF activators and inhibitors.

Original languageEnglish
Pages (from-to)974-979
Number of pages6
JournalCancer Treatment Reviews
Volume40
Issue number8
DOIs
Publication statusPublished - 2014

Keywords

  • BRAF
  • Cell signaling
  • MAPK
  • Molecular targeted therapy
  • NET
  • Neuroendocrine neoplasms
  • Neuroendocrine tumors
  • RAF
  • RAF-1

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging

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