Diving Into Cabazitaxel's Mode of Action: More Than a Taxane for the Treatment of Castration-Resistant Prostate Cancer Patients

Prostate cancer is a molecularly heterogeneous disease, and mechanisms of action of taxanes and potential mechanisms of resistance are not clearly defined. Taxanes are microtubule-stabilizing agents resulting in the slowing or blocking of mitosis at the metaphase-anaphase transition and induction of apoptotic cell death. Taxanes also can inhibit androgen receptor pathway. To date, several factors have been associated with taxane resistance, including alterations in tubulin, the effect of drug efflux pumps, and the dysfunctional regulation of signaling pathways that may be involved in resistance to therapy. Preclinical and clinical data support the distinct activity of cabazitaxel in prostate cancer that may overcome resistance to prior taxanes or hormonal therapies. It is challenging to define the most adequate therapeutic sequence for each patient. Moreover, the identification of molecular markers of resistance may help to select patients for specific therapies. (C) 2015 Elsevier Inc. All rights reserved.