Novel Biomarkers Assessment in the Progression from Androgen Dependent Prostate Cancer to Androgen Independent Prostate Cancer

Prostate cancer is the most commonly diagnosed form of cancer and the second leading cause of cancer-related death in males. Treatment with androgen ablation therapy after radical prostatectomy (RP) eventually leads to relapse and development of androgen-independent disease. Patients with androgen independent prostate cancer experience high morbidity and morality. At present, the ability to monitor the transformation to hormone independence at the earliest stages is inadequate and there is a desperate search for sensitive detection and monitoring methods to improve disease management and provide the most effective treatment strategies for these high risk patients. Progression from androgen dependent cancer to the more fatal androgen independent prostate cancer is a multi-step process involving androgen receptor (AR) and its associated growth regulatory signal transduction pathways. A highly sensitive, selective, noninvasive screening assay is needed to diagnose the development of hormone refractory prostate cancer and to monitor effectiveness of treatment or recurrence. We propose to identify the differential glycoprotein signatures from androgen-dependent LnCAP and androgen-independent PC3 cancer cells and complement their analysis with a comparison of glycoproteins identified in serum samples from hormone sensitive and refractory prostate cancer patients. Both the proteins and glycoforms of the proteins will be identified using glycoproteomics technologies developed by Drexel and Immunotope. Because the majority of glycoproteins are either surface-expressed or secreted, the panel of glycoproteins that we identify will be confirmed by the analysis of surface expression on circulating tumor cells (CTC) and/or detected specifically in the serum from patients with androgen-independent prostate tumors by comparing samples from androgen dependent patients. The identification of a panel of glycoproteins with modified glycan signatures will pave the way to the development of sensitive and selective hormone refractory prostate cancer specific diagnostic assays useful for rapid screening of large patient populations.