RESEARCH Q u a n t i t a t i v e Differences Permit- Chemical Combinations to Kill; Cancer Ceils
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Chemicals Team up Against Cancer Fight against cancer now includes combining different chemicals along with other techniques V v HEN bacteria develop resistance to one d r u g , physicians have b e e n forced to p u t t h e patient on another drug. But recently researchers have asked: Why wait until resistance develops? W h y not use a combination in t h e first place a n d kill the bacteria before resistance e v e r develops? A n u m b e r of researchers are applying this i d e a to cancer. A m o n g them is Daniel M. Shapiro of Columbia-Presbyterian Medical Center in N e w York.
In lab tests lie finds the mixtures of chemicals—a.s insny as four—can damage cancer cells markedly. Also, he finds that chemical combinations with radiation and/or surgery can cure more cases of experimental cancer. • Enzymes, P o i n t of Attack. Shapiro explains effectiveness of these combinations this w a y : Normal cells and cancer cells ha*ve the same kinds of enzymes, b u t tbtey differ in that many of the enzymes in the cancer cells are
present in lower concentrations. It is this quantitative biochemical difference that provides a way for enzyme antagonists to attack cancer cells. A specific antagonist blocks the same number of units of the particular enzyme in both normal and cancer cells. But in normal cells this enzyme pathway continues to work effectively since enzyme concentration is still high. The cancer cell, by contrast, is injured because the enzyme p a t h w a y is now severely depleted. Cancer cells have t o b e destroyed to cure cancer. B y combining several antagonists, several metabolic pathways are damaged a t the same time and t h e cells killed. This approach. Shapiro continues, kills cancer cells, since they have low enzyme concentrations. As no single normal tissue has the same over-all pattern of low enzymes as does cancer, normal tissues are slightly injured and recover after therapy is stopped. In light of his work on combina tions, Shapiro thinks that many chemicals screened alone for anticancer activity a n d discarded should b e re-evaluated. Those known t o act against lowactivity enzymes in cancer tissue might still b e of value in combinations. • C o m p l e t e Chemical Cures—Later. Shapiro foresees complete chemical cures of cancer within the lifespan of today's adult generation. But the chemicals now available are too toxic, so chemicals need an assist. About a year ago, Shapiro found that cancerous mice respond dramatically to a chemical combination plus radiation. One of the chemicals, 8-azaguanine, is known to b e toxic to humans, so he turned to another purine antimetabolite, 6-mercaptopurine ( 6 - M P ) , which is used to treat leukemia in h u m a n s With it, h e uses his newest a n d most promising anticancer compound, 6aminonicotinamide ( 6 - A N ) , developed by Willard Johnson of Frank Horner. Ltd., in Montreal. In collaboration with radiologist Morton M. Kligerman, Shapiro has cured breast tumors in 86
