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Review ArticleReviewsR

Sphingosine Kinase Inhibitors as Maintenance Therapy of Glioblastoma After Ceramide-Induced Response

LAURA A. SORDILLO, PETER P. SORDILLO and LAWRENCE HELSON
Anticancer Research May 2016, 36 (5) 2085-2095;
LAURA A. SORDILLO
SignPath Pharma, Inc., Quakertown, PA, U.S.A.
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PETER P. SORDILLO
SignPath Pharma, Inc., Quakertown, PA, U.S.A.
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LAWRENCE HELSON
SignPath Pharma, Inc., Quakertown, PA, U.S.A.
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Abstract

Ceramide and sphingosine 1-phosphate (S1P) are sphingolipid metabolites with important signaling functions. Ceramides promote apoptosis, whereas S1P favors proliferation, angiogenesis and cell survival. The balance between these opposing signaling functions is referred to as the sphingolipid rheostat. A shift in this balance toward S1P is seen in glioblastoma (GBM) and other cancers, and results in tumor cell survival and resistance to chemotherapy. Sphingosine kinase (SK), the enzyme responsible for transforming sphingosine into S1P, plays the critical role in modulating the balance between S1P and ceramides. Chemotherapeutic agents or radiation therapy may induce short-term responses in GBM patients by increasing ceramide levels. However, we believe that the enzyme SK may cause the increased ceramide to be metabolized to S1P, restoring the abnormally high S1P to ceramide balance, and that this may be part of the reason for the near-100% recurrence rate of GBM. The use of maintenance therapy with an SK inhibitor, in patients with GBM who have tumor reduction or stable disease after therapy, should be investigated.

  • Glioblastoma
  • maintenance therapy
  • tumor recurrence
  • sphingosine kinase
  • sphingosine 1-phosphate
  • ceramide
  • chemotherapy
  • sphingolipid rheostat
  • review
  • Received March 4, 2016.
  • Revision received April 12, 2016.
  • Accepted April 13, 2016.
  • Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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Anticancer Research: 36 (5)
Anticancer Research
Vol. 36, Issue 5
May 2016
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Sphingosine Kinase Inhibitors as Maintenance Therapy of Glioblastoma After Ceramide-Induced Response
LAURA A. SORDILLO, PETER P. SORDILLO, LAWRENCE HELSON
Anticancer Research May 2016, 36 (5) 2085-2095;

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Sphingosine Kinase Inhibitors as Maintenance Therapy of Glioblastoma After Ceramide-Induced Response
LAURA A. SORDILLO, PETER P. SORDILLO, LAWRENCE HELSON
Anticancer Research May 2016, 36 (5) 2085-2095;
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Keywords

  • Glioblastoma
  • Maintenance therapy
  • tumor recurrence
  • sphingosine kinase
  • sphingosine 1-phosphate
  • Ceramide
  • chemotherapy
  • sphingolipid rheostat
  • review
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