Changes in the serum proteome associated with docetaxel chemotherapy

Abstract

20036 Background: Trapeze is a randomised phase II clinical study involving Docetaxel chemotherapy ± Zoledronic Acid and strontium 89 for the treatment of hormone refractory prostate cancer. A proteomic sub-study is designed to identify novel biomarkers to monitor treatment. Methods: Surface-Ehanced Laser Desorption/Ionisation (SELDI) time-of-flight mass spectrometry combines retentate chromatography and mass spectrometry in a high-throughput platform for proteomic profiling of biological samples. A biofluid such as serum is applied to a ‘proteinchip array’, certain proteins will bind and non-binding species are removed by washing. The bound proteins are vaporised using a laser and detected by mass spectrometry. The peak intensities in the resulting “profiles” can be compared between patient cohorts to identify potential biomarkers. Results: The serum from 6 patients was analysed both before and after 2 cycles of chemotherapy using copper loaded IMAC30 proteinchip arrays. The intensities of 103 peaks were compared between pre- and post-treatment and 11 were found to differ significantly (p < 0.01, paired t-test). Hierarchical clustering was able to distinguish pre- and post-treatment sera. Initial results show these changes to continue in sequential samples taken from the same patient. Conclusions: Chemotherapy produces significant and detectable changes in the serum proteome. This is a significant difference from a recent lung cancer study carried out in our Institution (submitted separately), which showed no detectable changes in pre and post operative lung cancer patients once acute post-operative changes had settled. Work is currently underway to identify the discriminatory proteins in the SELDI profiles. The current Trapeze study accrual rate of approximately 10 patients per month will mean that 80 patients will be included in this treatment cohort by May 2006 and subject to initial findings, individual proteins of interest will be identified and followed throughout the phase II and subsequent phase III to determine if they can be used to assess patients individual response to chemotherapy and provide a biomarker to monitor prostate cancer therapy. No significant financial relationships to disclose.