Pharmacology & therapeutics
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It would be expected that drugs directed at the rate-limiting step in a key metabolic pathway in tumor cell proliferation would provide a useful basis for therapy of neoplasms. Ribonucleotide reductase catalyzes the rate-limiting step in the de novo synthesis of dNTP's for DNA synthesis. ⋯ As a result, combinations of drugs specifically directed at each of the subunits of ribonucleotide reductase have been shown to cause synergistic inhibition of L1210 cell growth in culture and synergistic cell kill. This approach offers a novel basis for the design of combination chemotherapy.