Increase in tumor GADD153 mRNA level following treatment correlates with response to paclitaxel

Purpose: We investigated the relationship between the basal and treatment-i nduced change in the tumor expression of the drug resistance gene MDR1 and the cellular injury response gene GADD153, and clinical response to paclita xel treatment. Methods: MDR1 and GADD153 mRNA levels were measured by rever se transcriptase polymerase chain reaction (RT-PCR) in tumor samples obtain ed by fine needle aspiration biopsy from 14 patients before and 24 h after paclitaxel infusion. Results: There was no difference between responders an d non-responders with respect to either the basal MDR1 mRNA level or the ch ange in MDR1 mRNA level at 24 h after treatment (P = 0.464). Likewise. ther e 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 inc rease 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 ma nifest 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.