The alkylating agents were the first drugs to be developed which killed cancer cells. John Cairns explains (17) how they "originated with the observation that one of the long term effects of the mustard gases used in WW1 was damage to the bone marrow." Doctors noticed that exposed soldiers and workers experienced a dramatic lowering of their white blood cell count and suggested the chemicals as a possible treatment for leukemia and lymphoma - cancers characterized by an overproduction of white blood cells. In his book Cytotoxic Drugs in the Treatment of Cancer (1969), E. Boesen describes how "the nitrogen mustards were themselves originally submitted for clinical trial as a result of studies that had been made of their toxic effects in man. They were not discovered by any test system." The comparative success of the (still used) nitrogen mustards provided the incentive to develop further alkylating agents.
Another example is the corticosteroid drugs. With cortisone modifying the signs and symptoms of so many diseases, it was natural that it would be tried in cancer patients. Only later was it tested on animal tumors.18 Nevertheless, there were clues from clinical studies of Cushing's Syndrome that suggested cortisone would be effective against human cancer. Cushing's Syndrome is characterized by excessive production of cortisone from the adrenal gland leading to a decrease in some body tissues including muscle wastage. Cortisone's action on muscle tissue suggested that it could also be effective against cancer tissue. The success of cortisone led to the development of closely related steroids such as prednisone, a very useful drug despite proving useless against a variety of animal cancers.(19)
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