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Vitamins versus leukemiaVitamins A and D may stop cancer cells from growing by Joseph Briante Vitamins that can "steer" cancer cells away from growth toward cell differentiation or cell death may form the basis of new therapies for fighting leukemia, say University of Guelph researchers. Profs. Kelly Meckling-Gill and Jim Kirkland, graduate student Donna Berry and post-doctoral fellow Ducica Curdic, Department of Human Biology and Nutritional Sciences, have discovered a vitamin D signalling pathway that affects how cancer cells grow and develop.They're now looking at a combination of vitamins A and D to combat acute promyelocytic leukemia (APL), which accounts for about 10 per cent of leukemia cases.Vitamins A and D may also have preventive activity in inhibiting leukemia development in the "at risk" population."If we treat leukemia cells with both (Vitamin A and D), those cells are induced to die at a high rate," says Meckling-Gill. "And the vitamins may have a role in preventing cancerous development."THE APL CHALLENGEAPL usually strikes adults in the prime of their life, with a median age of about 35. Traditional chemotherapy is effective, but relapses are common and very aggressive. So physicians use another approach known as differentiation therapy, which uses an agent to force immature cancer cells to mature and, at the same time, inhibits their growth. One such agent, retinoic acid -- an active metabolite of vitamin A -- has already been used clinically to treat APL. But its use is limited because it has only short-term efficacy, and patients generally develop resistance. The Guelph researchers hope that a dual attack using calcitriol, the active form of Vitamin D, and retinoic acid will improve the efficacy of differentiation therapy. If this happens, a treatment could be developed to use when retinoic acid fails.Meckling-Gill has shown that when calcitriol is used, APL cells mature normally in a pathway distinct from the one induced by retinoic acid. APL cells are arrested at a point where they would normally choose between two maturation pathways. Retinoic acid stimulates maturation to neutrophils; and calcitriol, to monocytes and macrophages, cell types important for immune function."A patient resistant to retinoic acid may still respond to vitamin D," says Meckling-Gill. "We hope this research will contribute to the design of a drug to use in a clinical setting." A MORE GENTLE THERAPYThe advantage of vitamin-derived treatment is that it could decrease problems associated with immunosuppressive and chemotherapeutic drugs, which often have very toxic side effects. If effective, differentiation therapy eliminates the need for patients to undergo bone marrow transplants, which are risky and costly.This research is sponsored by the Natural Sciences and Engineering Research Council and the Cancer Research Society Inc.