Taxanes appear to have significant clinical activity in
hormone-refractory
prostate cancer and are entering increasing numbers of clinical trials. In general, they appear to initiate the apoptotic process by binding to
beta-tubulin and promoting its polymerization. However, it is possible, at least in
prostate cancer cell lines, that the ultimate decision for or against apoptosis may be modulated by a number of factors, including levels of Bcl-family members, especially the antiapoptotic
proteins bcl-2 and bcl-xL. Differences in the cellular pharmacology of
docetaxel (
Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) and
paclitaxel have been identified.
Docetaxel has a somewhat higher affinity for microtubules than
paclitaxel (approximately twofold), and in some circumstances may be a more potent inducer of bcl-2 phosphorylation. However, it is not clear whether these
docetaxel-induced events are directly related to its antiprostate
cancer effects. In murine macrophages,
paclitaxel, but not
docetaxel, induces several proinflammatory genes, but it is not known whether this occurs in
prostate cancer cells. The mechanisms of cytotoxicity of
taxanes in
prostate cancer are undoubtedly complex and will require considerable additional study to fully understand.