taxane

Taxane is a class of diterpenoid compounds produced by plants of the genus Taxus (yew trees). The best-known taxanes are paclitaxel, docetaxel, and cabazitaxel. They share a common taxane skeleton and strong cytotoxic activity against dividing cells.

Mechanism of action is to bind to beta-tubulin in microtubules and stabilize them, preventing depolymerization. This disrupts normal spindle dynamics, leading to mitotic arrest and apoptosis in rapidly dividing cells. Their activity underlies their use as chemotherapy agents in several cancers.

Major members and origins: paclitaxel (Taxol) was isolated from Pacific yew trees in the 1960s and developed into a widely used anticancer drug. Docetaxel (Taxotere) is a semi-synthetic derivative related to 10-deacetylbaccatin III. Cabazitaxel (Jevtana) is a newer semi-synthetic taxane used after progression on other taxanes.

Clinical use: taxanes are employed to treat ovarian and breast cancers, non-small cell lung cancer, pancreatic cancer (paclitaxel, including nanoparticle albumin–bound formulations), and head and neck cancers, among others. Docetaxel is used for breast, NSCLC, and prostate cancer. Cabazitaxel is approved for metastatic castration-resistant prostate cancer after docetaxel treatment.

Formulations and safety: paclitaxel is often formulated with Cremophor EL, which can cause hypersensitivity reactions; premedication is common. Nab-paclitaxel uses an albumin-bound formulation to avoid Cremophor. Common adverse effects include myelosuppression, neuropathy, fatigue, mucositis, and alopecia; fluid retention and skin/nail changes can occur with some regimens.

Pharmacology and resistance: metabolism is primarily hepatic, with potential interactions via cytochrome P450 enzymes; resistance can arise from tubulin mutations or drug efflux mechanisms.