gms | German Medical Science

27th German Cancer Congress Berlin 2006

German Cancer Society (Frankfurt/M.)

22. - 26.03.2006, Berlin

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Prospective study of glucocorticoid co-medication and risk of resistance toward cancer therapy in solid tumor specimen, cell lines and xenografts

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  • corresponding author presenting/speaker Ingrid Herr - Universitätsklinikum, Heidelberg, Deutschland
  • Nikolaus Gassler - Universitätsklinikum, Heidelberg
  • Markus Büchler - Universitätsklinikum, Heidelberg
  • Helmut Friess - Universitätsklinikum, Heidelberg
  • Hendrik Dienemann - Universitätsklinikum, Heidelberg
  • Markus Hohenfellner - Universitätsklinikum, Heidelberg
  • Alexander Marme - Universitätsklinikum, Tübingen
  • Klaus-Michael Debatin - Universitätsklinikum, Ulm
  • Peter Krammer - DKFZ, Heidelberg
  • Peter Altevogt - DKFZ, Heidelberg
  • Hermann-Josef Groene - DKFZ, Heidelberg
  • Chengwen Zhang - DKFZ, Heidelberg

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO427

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dkk2006/06dkk537.shtml

Published: March 20, 2006

© 2006 Herr 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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Purpose: Glucocorticoids (GCs) are widely used in cancer therapy due to multiple benefits. Some reports have been associated co-medication of GCs with an increased risk of resistance toward cytotoxic therapy in solid tumors. It is not clear, whether this happens occasionally or commonly in carcinomas.

Experimental Design: Clinically used GC derivatives were combined with various cytotoxic treatments and the effect on apoptosis, viability and cell cycle of carcinomas was evaluated using more than 150 fresh surgical specimen, xenografts on mice and established cell lines of a representative spectrum of human solid malignant tumors. Comparative DNA-array analysis was performed to examine GC effects in carcinoma as compared to hematological tumor cells.

Results: Several clinically used GC derivatives inhibited the efficacy of a variety of cytotoxic anticancer agents in 91% of established cell lines, in 82% of surgical specimen and in all of five examined xenografts of solid malignant tumors. These results are in striking contrast to hematological cells where GCs induce apoptosis. GC-induced resistance occured at clinically achievable peak plasma levels and below, lasted for a long time, but was reversible. By DNA-array analysis of carcinoma and lymphoid cells we found differential expression of molecules involved in apoptosis and signal transduction as the cause of cell type specific effects. Two non-steroidal anti-emetic agents – a serotonin (5-HT3) and a neurokinin (NK1) receptor antagonist did not counteract anticancer treatment in the current setting.

Conclusions: Thus, at present, the question arises: should patients with malignant solid tumors be treated routinely with GCs?

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