Predictive Biomarkers of Response to Bc1-2 Biomodulation by G3139 and Docetaxel in Hormone-Refractory Prostate Cancer

2003 ◽  
Author(s):  
Anthony W. Tolcher
Keyword(s):  
Prostate Cancer ◽  
Predictive Biomarkers ◽  
Hormone Refractory Prostate Cancer ◽  
Hormone Refractory

Identification of candidate biomarkers of therapeutic response to docetaxel in hormone-refractory prostate cancer by proteomic profiling

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11010-11010
Author(s):  
L. Horvath ◽  
L. Zhao ◽  
B. Lee ◽  
D. Brown ◽  
M. Molloy ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Plasma Levels ◽  
Therapeutic Targets ◽  
Predictive Biomarkers ◽  
Protein Profiling ◽  
Hormone Refractory Prostate Cancer ◽  
Psa Response ◽  
Pc3 Cells ◽  
Hormone Refractory

11010 Background: Docetaxel (DTX)-based chemotherapy improves symptoms and survival in men with advanced hormone-refractory prostate cancer (HRPC). However, approximately 50% of patients do not respond to DTX but are exposed to significant toxicity without direct benefit. This study aimed to identify novel therapeutic targets and predictive biomarkers of DTX-resistance in HRPC. Methods: Protein profiling using iTRAQ mass spectrometry compared the PC3-Rx and DTX-sensitive PC3 cells and DTX-resistant PC3-Rx developed by DTX dose-escalation. Functional validation experiments were performed using recombinant protein treatment and siRNA knockdown experiments. Plasma/serum samples were collected from 41 men with metastatic HRPC treated with DTX-based chemotherapy (36 with paired samples pre- and post- cycle 1 DTX). Serum/plasma levels of MIC-1 were measured by ELISA. The association between MIC-1 levels, PSA response and overall survival (OS) were assessed by non-parametric tests and Kaplan-Meier survival analysis. Results: The IC50 for DTX in PC3-Rx was 10-fold higher than that in parent PC-3 cells. Protein profiling identified that MIC-1 levels were elevated 2.4 fold and AGR2 decreased 2.4 fold in DTX resistant cells. Knockdown of AGR2 expression in PC3 cells resulted in increased DTX resistance (p=0.03). PC-3 cells treated with recombinant MIC-1 also became resistant to DTX (p=0.001). Conversely, treating PC3-Rx cells with MIC1-siRNA restored sensitivity to DTX (p=0.002). In HRPC patients, pre-treatment MIC-1 levels did not correlate with PSA response to treatment (p=0.6). In contrast, increased serum/plasma levels of MIC-1 after cycle one of chemotherapy were associated with DTX resistance (p=0.006) and shorter overall survival (p=0.002). Conclusions: These results suggest that both AGR2 and MIC-1 play a role in DTX resistance in HRPC. Furthermore, changes in serum/plasma MIC-1 levels are associated with DTX resistance in a correlative human cohort. While a larger study is needed to validate these findings, the data provide evidence that MIC-1 as a potential predictive biomarker and both MIC-1 and AGR2 are potential therapeutic targets in DTX resistance. No significant financial relationships to disclose.

604: A Phase I Trial of Vaccination of Personalized Peptides for HLA-A2/A24 Positive Patients with Hormone-Refractory Prostate Cancer

2007 ◽  
Vol 177 (4S) ◽  
pp. 202-202
Author(s):  
Hirotsugu Uemura ◽  
Motoyoshi Tanaka ◽  
Shigeya Uejima ◽  
Takafumi Minami ◽  
Kiyohide Fujimoto ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase I ◽  
Phase I Trial ◽  
Hormone Refractory Prostate Cancer ◽  
Hormone Refractory

829: PSA-Flare up in Docetaxel Therapy of Hormone-Refractory Prostate cancer (HRPCA): Incidence and Clinical Impact?

2005 ◽  
Vol 173 (4S) ◽  
pp. 225-225
Author(s):  
Peter Olbert ◽  
Andres J. Schrader ◽  
Axel Hegele ◽  
Zoltan Varga ◽  
Axel Heidenreich ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Impact ◽  
Hormone Refractory Prostate Cancer ◽  
Hormone Refractory
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