Mechanisms of resistance to docetaxel and therapeutic strategy

Docetaxel is the stan- dard treatment for metastatic castration-resistant prostate can- cer (mCRPC) patients, but its effec- tiveness is limited in time and tumor escape the inevitable. The various combinations with doceta- xel were negative in terms of prolongation of overall survival. A better understanding of mecha- nisms of docetaxel resistance on microtubule and p-glycoprotein, for instance, would guide the therapeutic strategy. After the administration of docetaxel, caba- zitaxel, abiraterone, alpharadin and recently MDV3100 have shown their effectiveness in im- proving overall survival compared to a placebo or mitoxantrone in phase III trials. Also in pre- docetaxel stage, sipuleucel-T has proven effective in asymptomatic mCRPC patients. The identifica- tion of predictors of response to taxanes will personalize chemo- therapy to induce durable res- ponse and significantly prolonged survival. To cite this journal: Oncologie 14 (2012).