Drug Development and Screening

Abstract

The present generation of anti-cancer drugs have been developed from a variety of different backgrounds. Stemming from toxicological studies on the effects of sulphur mustard gas as used in World War I, the modern era of cancer chemotherapy began in the 1940s with the demonstration that nitrogen mustard produced responses in malignant lymphoma. At about the same time, the antibacterial activity of para-aminobenzene sulphonamide was shown to be due to the fact that it was an analogue of the natural metabolite, para-aminobenzoic acid, and lead to the concept of metabolite—antimetabolite interactions. This, in turn, resulted in the synthesis of folic acid analogues, when low serum folate levels were noted in children with acute lymphoblastic leukaemia. By 1948, it had been shown that aminopterin (a folate analogue) could produce remissions in children with acute lymphocytic leukaemia, and there was increasing confidence that chemical substances were capable of controlling cancer in man. There followed a tremendous surge of interest in the development of methods to design and test compounds for antineoplastic activity, resulting, thirty years later, in the present drug development programmes which test many thousand new compounds each year. This chapter outlines the current approach to developing new anti-cancer drugs from their synthesis, screening for antineoplastic activity, toxicological evaluation to formulation and preparation for clinical trial.