title: Emerging targets to monitor and overcome docetaxel resistance in castration resistant prostate cancer (review).
abstract: Drug development for castration resistant prostate cancer (CRPC) is challenging, since this cancer is still associated with high mortality and limited therapeutic options. In 2004, docetaxel became the first-line chemotherapy for CRPC improving survival by a few months and remains the standard of care in CRPC patients. However, existing or developing resistance to docetaxel in patients is the main limitation of its efficacy. The present review presents the molecular mechanisms involved in docetaxel toxicity and in docetaxel resistance in prostate cancer cells. We outlined the endogenous mechanisms of resistance and the role of tumor microenvironment in the resistance of CRPC to docetaxel. This has led us to focus on molecules associated with resistance, such as the molecular chaperones heat shock proteins (HSPs) and clusterin (CLU), and the cytokines interleukin-6 (IL-6) and the divergent member of the tumor growth factor family MIC-1 (macrophage inhibitory cytokine-1 also named GDF-15). We discuss their interest as blood-based markers to monitor docetaxel resistance. Finally, new therapies intended to overcome docetaxel resistance of CRPC targeted on these molecular resistance pathways are present.
authors: EA 7269 Ecole Pratique des Hautes Etudes-University of Burgundy-INSERM U866, Dijon 21079, France.
authors: L
authors: L
authors: Magadoux
authors: EA 7269 Ecole Pratique des Hautes Etudes-University of Burgundy-INSERM U866, Dijon 21079, France.
authors: N
authors: N
authors: Isambert
authors: EA 7269 Ecole Pratique des Hautes Etudes-University of Burgundy-INSERM U866, Dijon 21079, France.
authors: S
authors: S
authors: Plenchette
authors: EA 7269 Ecole Pratique des Hautes Etudes-University of Burgundy-INSERM U866, Dijon 21079, France.
authors: J F
authors: JF
authors: Jeannin
authors: EA 7269 Ecole Pratique des Hautes Etudes-University of Burgundy-INSERM U866, Dijon 21079, France.
authors: V
authors: V
authors: Laurens
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood; D045744:Cell Line, Tumor; D051152:Clusterin / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D055436:Growth Differentiation Factor 15 / Q000037:antagonists & inhibitors / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D043823:Taxoids / Q000627:therapeutic use; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D051152:Clusterin; D055436:Growth Differentiation Factor 15; D006360:Heat-Shock Proteins; D043823:Taxoids; D000077143:Docetaxel