Part V. Use of combinations of antimetabolites for chemotherapy of cancer

It is possible to view the approach to a chemotherapy of cancer more rationally if it is given a frame derived from a recent concept of how cancer arises and progresses. This concept will be referred to as the "deletion concept." The experimental evidence for this concept is available mainly from studies on chemical carcinogenesis and has been discussed elsewhere. 16, 20-22 By this concept, a cancer cell arises when a normal call is subject to deletions that are not lethal, but leave it without the components responsive to normal growth controls. What specific deletions are necessary to achieve this result are as yet unknown. It may be that the same net result can be reached by any of several different deletions. Potter21 has suggested one plausible way in which this could occur and cites several examples. When cells have alternate metabolic pathways such that a substrate can be either catabolized for energy or used to synthesize new material for cell growth, the deletion of the catabolic pathway could lead to uncontrolled growth. One example cited is that of uracil, which can be used by liver cells to synthesize uracil nucleotide