The development of methotrexate, a widely used drug for the treatment of leukemia and other cancers, is a further triumph of the clinical method. Methotrexate belongs to a class of drugs known as folic acid antagonists, whose therapeutic potential was discovered by Farber during his attempts to treat leukemia.(20) Researchers had shown that folic acid, a member of the vitamin B complex, inhibited the growth of tumors in mice and, although the effect could not be confirmed in other laboratories, Farber nevertheless decided to test the drug in clinical trials. But contrary to the original animal experiments, folic acid actually made the leukemia worse! Farber reasoned that the desired effect might still be achieved by using drugs - "antagonists" - that blocked or opposed the action of folic acid.
The idea was to choose antagonists which so resembled the folic acid that cancer cells would be fooled into believing that they were the vitamin necessary for growth, when in fact they had no nutritional value at all. On the contrary, the antagonists would prevent the folic acid from reaching the cell, which would then be unable to grow. Without any preceding animal experiments, Farber tested a variety of folic acid antagonists on children with leukaemia, an illness whose prognosis had hitherto been grim. The results were very encouraging and provided the incentive to develop further antagonists, including Methotrexate.
The laboratory mouse is cheap and commonly used in cancer research, but the data produced is often inapplicable to the human disease.
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