R

Fig. 20.2 Chemical structures of representative chemotherapeutic agents useful in clinical cancer chemotherapy.

apies been shown effective in the treatment of neoplastic disease. The principal effective agent is all-trans-retinoic acid (ATRA), which has been found especially effective in the treatment of acute promyelocytic leukemia (Fenaux et al., 1997). Unfortunately, this differentiation therapy with retinoids has not been very effective in other types of neoplasms, but it has shown some degree of efficacy as one of a number of retinoids effective in chemoprevention. In addition to specific chemicals, both synthetic and natural, several different enzymes have also been utilized in the chemotherapy of neoplasia, based at least in part on their ability to metabolize and eliminate specific metabolites, usually amino acids, essential for the growth of specific neoplastic cells (Chapter 8). Primary among these agents is the enzyme produced by Escherichia coli, L-asparaginase, which catalyzes the conversion of the amino acid L-asparagine to aspartic acid. By its catalytic action, the enzyme rapidly and completely depletes circulating pools of L-aspar-agine in the organism, thus compromising any cells that are unable or ineffective in synthesizing

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