Summary of informal discussion on the basis for future approaches to cancer chemotherapy.

Following the presentations on the design of new therapeutic agents, Dr. Mandel opened the discussion by remarking on the extensive progress that has been made in the past years in directing the synthesis of new drugs. Whereas formerly the availability of new chemicals frequently was limited by the technics for preparation of compounds of new structures or modified functional groups, our improved understanding of the requisites for interaction with specific enzymes now is playing an ever increasing role in the design of chemical structures with greater therapeutic usefulness. Dr. Schepartz agreed with Dr. Heidelberger that greater effort should be devoted to the synthesis of antimetabolites than to alkylating agents. In both fields, however, new and useful drugs have emerged when the basic structures of the compounds were altered substantially, whereas empirical and minor changes, such as those in side chains, have been relatively unfruitful. Even with the alkylating agents, which have been quite thoroughly explored, new structures with altered biologic activity might still be uncovered. For instance, the large number of methanesulfonates in the past have demonstrated rather restricted activity in experimental tumor systems or in man, but more recent derivatives such as those from Dr. Sakurai's laboratory, have begun to show high