Vinca Alkaloids as Chemotherapeutic Agents Against Breast Cancer

Abstract Worldwide, breast cancer is the second most common cancer after lung cancer and it is the first most incident and prevalent cancer in women. Plant-derived natural products have historically been in drug discovery process as a source of chemotherapeutic agents against different kinds of cancers, including breast cancer. More than half of the anticancer drugs used in clinical uses have presently a natural origin. In this context, vinca alkaloids (vinblastine and vincristine), isolated from the Madagascar periwinkle plant Catharanthus roseus G. Don. (Apocynaceae), were the first natural products with potent antitumor properties for clinical use. Their main mechanism of action is related to their ability to interfere with the mitotic spindle apparatus and thus to trigger cellular arrest in metaphase during mitosis and consequently to cause apoptosis and tumor cell death. On the basis of the pharmacological interest of vinca alkaloids as anticancer agents, there have been developed semisynthetic analogs, including vinorelbine (5′-nor-vinca-alkaloid, modified on the catharanthine ring) and vinflunine (a bis-fluorinated vinorelbine derivative). Since the discovery of vinca alkaloids, both natural and synthetic origin, numerous clinical trials have been carried out to-date to evaluate the efficacy of these compounds against breast cancer. These anticancer agents are commonly used in combination chemotherapy regimens as well as a therapeutic option if other chemotherapy agents fail. The current chapter covers the historical outcome of vinca alkaloids, from the discovery of compounds of natural origin (vinblastine and vincristine) to the synthesis of analogs with anticancer activity (vinorelbine and vinflunine), together with a comprehensive review of the newest preclinical and clinical investigations on these compounds against breast cancer.