taxanes

Taxanes are a class of diterpenoid anticancer agents derived from the yew tree genus Taxus. The best known members are paclitaxel (Taxol) and docetaxel (Taxotere); a newer taxane, cabazitaxel (Jevtana), is used after progression on docetaxel.

Taxanes originate from natural products first isolated from Taxus brevifolia in 1971. Because yew bark supply is limited, they are produced by semisynthesis from 10-deacetylbaccatin III or via plant cell culture, enabling broader clinical use.

Taxanes stabilize microtubules by binding to beta-tubulin, preventing depolymerization. This disrupts mitotic spindle formation, causing arrest at the G2/M phase of the cell cycle and triggering apoptosis in cancer cells.

Paclitaxel and docetaxel are used in the treatment of ovarian, breast, and non-small cell lung cancers, among others. Cabazitaxel is approved for metastatic castration-resistant prostate cancer after prior docetaxel treatment. Administration is intravenous, typically on a 2- to 3-week schedule; premedication may be required for paclitaxel to mitigate hypersensitivity reactions.

Common adverse effects include neuropathy, neutropenia, fatigue, alopecia, mucositis, and hypersensitivity reactions. Paclitaxel uses Cremophor EL as a solvent, contributing to hypersensitivity risk, while docetaxel uses polysorbate 80, influencing tolerability and premedication needs.

Resistance to taxanes can arise from drug efflux by P-glycoprotein, tubulin mutations or isotype changes, and alterations in apoptotic pathways. To enhance efficacy and manage resistance, taxanes are often used in combination regimens and with dose adjustments based on tolerability.