14603 Background: EGFR (Epidermal Growth Factor Receptor) is a promising target in various epithelial cancers. Erlotinib is an orally active small molecule tyrosine kinase inhibitor (TKI) targeting EGFR, under evaluation in prostate cancer. To identify protein biomarkers associated with EGFR TKI treatment we performed serum protein profiling in advanced prostate cancer patients receiving erlotinib, using Surface Enhanced Laser Desorption/Ionization-Time of Flight Mass Spectrometry (SELDI-TOF MS). Method: Serums from 23 advanced or metastatic prostate cancer patients enrolled in a phase II study of erlotinib as single agent were collected before treatment, on D28 and D56 and kept frozen in liquid nitrogen until analysis. Serum samples from each patients and each time points were first urea treated and then incubated with 3 different ProteinChip arrays (Ciphergen Biosystems): IMAC-Cu, CM10 and H50 using a fully automated platform (Tecan). After adding SPA matrix, arrays were analysed using a PBSIIc ProteinChip reader (Ciphergen Biosystems). After noise reduction, baseline substraction, and data normalisation, protein peaks were detected using the Biomarker Wizard tool integrated to the ProteinChip Software 3.1. Numeric data were then exported to excel files that were used for further biostatistic processing. Results: Combining protein profiles resolved from each experimental condition, several hundreds of protein peaks were obtained. Protein profiles from untreated and D28 and D56-treated patients were compared using non-parametric statistical methods and several protein peaks appeared differentially expressed between pre and post-treatment samples. Supervised methods identified protein peaks correlating with specific erlotinib toxicity on day 28. Since only minimal activity was noted in this trial, no protein profile correlating with anti-tumor effect was identified. Purification and identification of proteins modulated by treatment and associated with toxicity are ongoing. Conclusion: Serum protein profiling using SELDI-TOF MS is a promising method to characterize pharmacoproteomics of innovative compounds under development and to identify protein biomarkers potentially associated with drug effects. No significant financial relationships to disclose.
Erratum: Serum protein profiling by SELDI mass spectrometry: detection of multiple variants of serum amyloid alpha in renal cancer patients
