Vinca Alkaloids, Taxanes & Anticancer Antibiotics

Introduction

• Natural-product cytotoxics are antineoplastics derived from plants, soil microbes (Streptomyces) or marine organisms; this topic covers two mechanistically opposite super-groups — microtubule-damaging "spindle poisons" (vinca alkaloids + taxanes) and antitumour antibiotics (anthracyclines, dactinomycin, bleomycin, mitomycin).
• Spindle poisons (vinca alkaloids, taxanes, eribulin, ixabepilone) act on the mitotic spindle in M phase — the most vulnerable phase of the cell cycle — and are cell-cycle–phase-specific.
• Anticancer antibiotics are microbial fermentation products that injure DNA (intercalation, topoisomerase-II poisoning, free-radical strand scission, alkylation) across several phases — relatively cycle-nonspecific.
• All share the proliferation-targeted dose-limiting host toxicities of cytotoxics: bone marrow, GI mucosa, hair follicles, gonads and the fetus. Tumours with a high growth fraction (leukaemias, lymphomas, germ-cell, paediatric tumours) are the most chemosensitive.