The development of cytotoxic chemotherapeutics in the twentieth century

Abstract

Although medicines have been obtained from natural products for millennia, extensive systematic studies to obtain anticancer agents through isolation from natural sources or through synthesis in the laboratory were attempted in the twentieth century. The same period also saw the development of animal models through which in vivo preclinical research could be conducted to examine the anticancer potential of chemicals, in addition to in vitro research. In the 1940s the era of modern cancer chemotherapy started with the introduction of the first classical chemotherapeutics; the first alkylating agents were obtained in the early 1940s and the first antimetabolites toward the end of the decade. In the 1950s scientists ventured out of the laboratory to discover natural products with anticancer potential. Since microorganisms, sessile terrestrial plants and marine invertebrates have evolved a large number of chemical defense mechanisms, it has been argued that some substances out of these might show anticancer activity. Tens of thousands of natural products derived from these organisms have been screened for anticancer activity primarily by the US since the 1950s. Vinca alkaloids introduced in the 1960s, anticancer antibiotics in the 1970s and taxanes in the 1990s are examples of the encouraging outcomes. In addition to local interventions such as surgery and radiotherapy, cancer chemotherapy based upon these therapeutic agents is available in medicine today as a systemic modality in the treatment of the disease.