Targeted cancer therapy: What if the driver is just a messenger?

Jonathan H. Schatz, Hans Guido Wendel

Research output: Contribution to journalReview article

12 Scopus citations

Abstract

"Shoot the driver" is the paradigm of targeted cancer therapy. However, resistance to targeted inhibitors of signaling pathways is a major problem. In part the redundancy of signaling networks can bypass targeted inhibitors and thereby reduce their biological effect. In this case the driver turns out to be one of several potential messengers and is easily replaced. Cocktails of multiple targeted inhibitors are an obvious solution. This is limited, however, by the lack of potent inhibitors and may also produce increased toxicity. Therefore we explored the direct blockade of a key biological activity downstream from multiple converging oncogenic signals. Specifically, several oncogenic signaling pathways including AKT, MAPK and PIM kinase signals converge on the activation of capdependent translation. In cancer cells, aberrant activation of cap-dependent translation favors the increased expression of short-lived oncoproteins like c-MYC, MCL1, CYCLIN D1 and the PIM kinases. Intriguingly, cancer cells are especially sensitive to even temporary reductions in these proteins. We will discuss our findings concerning translational inhibitor therapy in cancer.

Original languageEnglish (US)
Pages (from-to)3830-3833
Number of pages4
JournalCell Cycle
Volume10
Issue number22
DOIs
StatePublished - Nov 15 2011

Keywords

  • Cancer
  • Lymphoma
  • Targeted therapy
  • Translation
  • eIF4E

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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