Article
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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Published: | March 20, 2006 |
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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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