Preclinical mechanisms of action of docetaxel and docetaxel combinations in prostate cancer

Semin Oncol. 2001 Aug;28(4 Suppl 15):3-7. doi: 10.1016/s0093-7754(01)90148-4.


Docetaxel, a semisynthetic taxane, has exhibited significant single-agent activity against prostatic tumors. In phase I/II studies, single-agent docetaxel and the combination of docetaxel plus estramustine were effective in inducing prostate-specific antigen reductions of > or =50% in men with androgen-independent prostate cancer (AIPC). The underlying reason for docetaxel's clinical activity against prostate cancer has been a focus of ongoing research. Docetaxel is believed to have a twofold mechanism of antineoplastic activity: (1) inhibition of microtubular depolymerization, and (2) attenuation of the effects of bcl-2 and bcl-xL gene expression. Taxane-induced microtubule stabilization arrests cells in the G(2)M phase of the cell cycle and induces bcl-2 phosphorylation, thereby promoting a cascade of events that ultimately leads to apoptotic cell death. In preclinical studies, docetaxel had a higher affinity for tubulin and was shown to be a more potent inducer of bcl-2 phosphorylation than paclitaxel. Laboratory evidence also supports the clinical evaluation of docetaxel-based combinations that include agents such as trastuzumab and/or estramustine. The pathways for docetaxel-induced apoptosis appear to differ in androgen-dependent and androgen-independent prostate cancer cells. Further elucidation of these differences will be instrumental in designing targeted regimens for the treatment of localized and advanced prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Apoptosis
  • Cell Cycle / drug effects
  • Docetaxel
  • Drug Evaluation, Preclinical
  • Gene Expression Regulation, Neoplastic / drug effects
  • Genes, bcl-2
  • Humans
  • Male
  • Paclitaxel / administration & dosage
  • Paclitaxel / analogs & derivatives*
  • Paclitaxel / pharmacology*
  • Paclitaxel / therapeutic use*
  • Phosphorylation
  • Prostatic Neoplasms / drug therapy*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Taxoids*
  • Tubulin
  • Tumor Cells, Cultured
  • bcl-X Protein


  • Antineoplastic Agents, Phytogenic
  • BCL2L1 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Taxoids
  • Tubulin
  • bcl-X Protein
  • Docetaxel
  • Paclitaxel