gms | German Medical Science

27th German Cancer Congress Berlin 2006

German Cancer Society (Frankfurt/M.)

22. - 26.03.2006, Berlin

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Inhibition of TKTL1-Transketolase Offers New Therapeutic Strategies For Cancer Patients with Invasive Tumors or Metastases

Meeting Abstract

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  • corresponding author presenting/speaker Johannes F. Coy - R-Biopharm AG, Darmstadt, Deutschland
  • Sigrun Langbein - Universitätsklinikum, Mannheim
  • S. Langbein - Universitätsklinikum, Mannheim
  • Anette Steidler - Universitätsklinikum, Mannheim
  • Rainer Grobholz - Universitätsklinikum, Mannheim
  • Frank Willeke - Universitätsklinikum, Mannheim
  • Elmar Stickeler - Universitätsklinikum, Freiburg
  • Gerald Gitsch - Universitätsklinikum, Freiburg
  • Giorgio Stassi - Universität Palermo
  • Monica Zerilli - Universität Palermo
  • Martha Földi - Universitätsklinikum, Freiburg
  • Axel zur Hausen - Universitätsklinikum, Freiburg
  • Wilko Staiger - Universitätsklinikum, Mannheim
  • Nadine Lukan - Universitätsklinikum, Mannheim
  • Juliana Popa - Universitätsklinikum, Mannheim
  • Anette Steidler - Universitätsklinikum, Mannheim
  • Rainer Grobholz - Universitätsklinikum, Mannheim
  • Frank Willeke - Universitätsklinikum, Mannheim
  • Elmar Stickeler - Universitätsklinikum, Freiburg
  • Gerald Gitsch - Universitätsklinikum, Freiburg
  • Giorgio Stassi - Universität Palermo

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO016

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dkk2006/06dkk126.shtml

Published: March 20, 2006

© 2006 Coy et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Aggressive tumors and metastases are characterized by high glucose consumption and high lactate production, both indicating poor prognosis. The pentose phosphate pathway allows glucose conversion to ribose for DNA/RNA synthesis and glucose degradation to lactate. The non-oxidative part of the pentose phosphate pathway is controlled by transketolase enzyme reactions. We have detected a strong upregulation of a transketolase-like transcript (TKTL1) in human malignancies, whereas transketolase (TKT) and transketolase-like-2 (TKTL2) transcripts were not upregulated. TKTL1 protein over-expression was detected in a subset of carcinomas of the breast, bladder, lung, stomach, prostate, thyroid, ovarian, cervix, pancreas, kidney, and colon. TKTL1 protein expression was correlated to invasive colon, ovarian and bladder tumors and to poor patients outcome. TKTL1 encodes a transketolase with unusual enzymatic properties which are likely to be caused by the internal deletion of conserved residues. TKTL1 upregulation in tumors allows an enhanced, oxygen independent glucose usage and a lactate based matrix degradation. Since inhibition of transketolase enzyme reactions suppresses tumor growth and metastasis, TKTL1 represents the relevant target for novel anti-transketolase cancer therapies. We suggest a novel individualized cancer therapy which is based on an orally administered small compound specifically inhibiting TKTL1-transketolase and which might enable the targeted therapy of invasive tumors and metastases.