Chemotherapy of cancer

Abstract

Dr. Gilbert H. Mudge: The chemotherapy of malignant disease has been discussed with particular emphasis on the biology of cancer and the mechanisms of action of various chemotherapeutic agents. The metabolism of nucleic acids has been stressed because of their undoubtedly important role in the biologic reactions under consideration. Nucleic acids arc found in all living cells and may be divided into two main groups. The desoxypentose nucleic acids occur mainly within nuclei while the pentose nucleic acids are found chiefly within the cytoplasm. Their physical and chemical properties are briefly reviewed. Present evidence strongly indicates that nucleic acids represent the chemical basis of chromosomes and as such play a central role in the mitotic activity of both normal and malignant cells. The nitrogen mustards are unquestionably of great use in the treatment of certain types of malignancy. Their pharmacologic action is reviewed in relationship to chemical structure. These compounds react rapidly with a variety of chemical groupings. A careful analysis of minimally effective concentrations reveals mitotic activity to be the cell function most sensitive to their action. The evidence is reviewed which suggests a specific effect upon nucleoproteins. The analogues of folic acid represent another group of agents employed in the treatment of malignancy. Their use has permitted precise definition of the role of folic acid in hematopoiesis as well as in nucleic acid metabolism. Studies with aminopterin have revealed that it blocks intermediary reactions leading to the synthesis of nuclear proteins and that the metabolic block is competitive in type. The probable site of this block is discussed in relationship to the action of the citrovorum factor. A different aspect of cancer chemotherapy is discussed in relationship to the action of 8-azaguanine. This antimetabolite has a marked effect upon certain tumors but no effect upon others. In this instance it has been possible to demonstrate that the specificity of the drug action can be correlated with the metabolism of the tumor. Thus normal tissue and resistant tumors can inactivate the drug while sensitive tumors contain low concentrations of the inactivating enzyme. It is emphasized that the successful development and employment of chemotherapeutic agents for the treatment of cancer will depend upon further knowledge of the specific metabolic abnormalities of the malignant cell. The subtle differences in the biochemical makeup of different tumors makes it extremely improbable that any single drug will ever become a panacea for all cancers.