Cell cycle taxane effects

Although not a taxane, ixabepilone is a novel microtubule inhibitor that was recently approved for metastatic breast cancer in combination with the oral fluoropyrimidine capecitabine or as monotherapy. It is a semisynthetic analog of epothilone B, and is active in the M phase of the cell cycle. This agent binds directly to 6-tubulin subunits on microtubules, leading to inhibition of normal microtubule dynamics. Of note, this agent continues to have activity in drug-resistant tumors that overexpress P-glycoprotein or tubulin mutations. The main adverse effects include myelosuppression, hypersensitivity reactions, and neurotoxicity in the form of peripheral sensory neuropathy. 

Drugs that block cell-cycle progression prior to mitosis antagonize the toxic effects of taxanes. 

Paclitaxel binds specifically to /3-tubulin and antagonizes the disassembly of microtubules bundles of microtubules and aberrant structures derived from microtubules appear in the M phase of the cell cycle, causing mitotic arrest. Cell kilhng is dependent on both drug concentration and duration of cell exposure. Drugs that block cell cycle progression prior to mitosis antagonize the toxic effects of taxanes. 

Chemotherapy Cell cycle effects, modulation of proliferation kinetics Vinca alkaloids, methotrexate, platinum compounds, taxanes, doxorubicin Chabner et al. (1996)... 

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