Abstract
Purpose: We investigated the relationship between the basal and treatment-induced change in the tumor expression of the drug resistance gene MDR1 and the cellular injury response gene GADD153, and clinical response to paclitaxel treatment. Methods: MDR1 and GADD153 mRNA levels were measured by reverse transcriptase polymerase chain reaction (RT-PCR) in tumor samples obtained by fine needle aspiration biopsy from 14 patients before and 24 h after paclitaxel infusion. Results: There was no difference between responders and non-responders with respect to either the basal MDR1 mRNA level or the change in MDR1 mRNA level at 24 h after treatment (P = 0.464). Likewise, there was no difference in basal GADD153 mRNA level between responders and non-responders. However, there was a significantly greater increase in GADD153 mRNA at 24 h in responders compared with non-responders (P = 0.005). An increase in GADD153 mRNA level of 1.5-fold or higher predicted response with a sensitivity of 86% and a specificity of 100%. Conclusions: An increase in GADD153 mRNA level reflects chemotherapy-induced damage sufficient to be manifest as a clinically detectable reduction in tumor volume. Measurement of the change in GADD153 mRNA level successfully identified patients destined to respond as early as 24 h post-treatment.
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Received: 21 July 1999 / Accepted: 19 November 1999
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de las Alas, M., Christen, R., Gately, D. et al. Increase in tumor GADD153 mRNA level following treatment correlates with response to paclitaxel. Cancer Chemother Pharmacol 45, 381–388 (2000). https://doi.org/10.1007/s002800051006
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DOI: https://doi.org/10.1007/s002800051006