Chapter Six – Therapeutic Potential of Targeting SK1 in Human Cancers

Heba Alshaker, Lysann Sauer, Danielle Monteil, Silvia Ottaviani, Shyam Srivats, Torsten Böhler, Dmitri Pchejetski

Research output: Chapter in Book/Report/Conference proceedingChapter (peer-reviewed)

40 Citations (Scopus)

Abstract

Sphingosine kinase 1 (SK1) is a lipid enzyme with oncogenic properties that converts the proapoptotic lipids ceramide and sphingosine into the antiapoptotic lipid sphingosine-1-phosphate and activates the signal transduction pathways that lead to cell proliferation, migration, the activation of the inflammatory response, and the impairment of apoptosis. 

There is compelling evidence that SK1 activation contributes to cancer progression leading to increased oncogenic transformation, tumor growth, resistance to therapies, tumor neovascularization, and metastatic spread. High levels of SK1 expression or activity have been associated with a poor prognosis in several human cancers. 

Recent studies using cancer cell and mouse models demonstrate a significant potential for SK1-targeting therapies to synergize with the effects of chemotherapy and radiotherapy; however, until recently the absence of clinically applicable SK1 inhibitors has limited the translation of these findings into patients. With the recent discovery of SK1 inhibiting properties of a clinically approved drug FTY720 (Fingolimod), SK1 has gained significant attention from both clinicians and the pharmaceutical industry and it is hoped that trials of newly developed SK1 inhibitors may follow soon. 

This review provides an overview of the SK1 signaling, its relevance to cancer progression, and the potential clinical significance of targeting SK1 for improved local or systemic control of human cancers.

Original languageEnglish
Title of host publicationAdvances in Cancer Research
Subtitle of host publicationThe Role of Sphingolipids in Cancer Development and Therapy
EditorsJames S. Norris
PublisherElsevier
Pages143-200
Number of pages58
Volume117
ISBN (Print)978-0-12-394274-6
DOIs
Publication statusPublished - 2013

Publication series

NameAdvances in Cancer Research
PublisherElsevier
Volume117

Keywords

  • Animals
  • Antineoplastic Agents
  • Humans
  • Lysophospholipids
  • Mice
  • Neoplasms
  • Phosphotransferases (Alcohol Group Acceptor)
  • Signal Transduction
  • Sphingosine

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