Pancreatic neuroendocrine tumors

Mamatha Bhat, Peter Metrakos, Santiago Ramon Y Cajal, Nahum Sonenberg, Tommy Alain

Research output: Chapter in BookChapterResearchpeer-review

Abstract

© 2014 Springer Science+Business Media Dordrecht. All rights reserved. In two landmark phase III trials, the drugs everolimus and sunitinib demonstrated remarkable efficacy against pancreatic neuroendocrine tumors (PaNETs). Everolimus acts as a specific inhibitor of the mTOR complex 1 (mTORC1), which is often found to be hyperactivated in PaNETs. Sunitinib is a multitargeted inhibitor of RTKs, such as PDGFR, FGFR and VEGFR. These receptors are under frequent stimulation in PaNETs and result in the activation of the mTOR signaling pathway. When hyperactive, mTOR prompts a dysregulation in translation, especially at the initiation step of translation, and thus drives a tumorigenic program. Limiting the activity of mTOR with small molecular inhibitors can therefore prevent the dysregulated translation of mRNAs encoding factors with oncogenic or metastatic functions. Further strategies directly targeting translation initiation factors might be therapeutically effective in PaNETs. In this chapter, we review the common molecular and biochemical alterations in PaNETs and how they can lead to dysregulated translation. We also discuss novel therapeutic approaches vis-à-vis translation and its regulation in PaNETs.
Original languageEnglish
Title of host publicationTranslation and Its Regulation in Cancer Biology and Medicine
Pages631-643
Number of pages12
DOIs
Publication statusPublished - 1 Mar 2014

Keywords

  • Cell signaling
  • Everolimus
  • Neuroendocrine tumor
  • Pancreatic neuroendocrine tumor (PaNET)
  • Targeted therapy
  • Translation
  • eIF4E
  • eIF4E-binding protein (4E-BP)
  • mTOR inhibitor
  • mTOR pathway

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