The new therapeutic approach involves combining a chemotherapeutic drug used to treat cancer with a new experimental drug called an IDO inhibitor. IDO is an enzyme that blocks the ability of the immune system to eliminate foreign or abnormal cells such as cancer cells. In pre-clinical studies, the researchers found that IDO inhibitors dramatically improve the ability of chemotherapy to destroy breast tumors. Two potential advantages of the approach is that it marries to standard chemotherapeutic practices, easing adoption, and that it is well-suited to attack disseminated metastatic disease, the overarching challenge faced by cancer patients.

The new approach emerged from Drs. Muller and Prendergast's studies of Bin1, an anti-cancer gene that they found to control IDO. Muller notes that the new approach would have been missed by the usual means of discovering new cancer drugs. "IDO inhibitors are not intrinsically toxic to cancer cells," he explained. "Most new cancer drugs are discovered by evaluating how effectively they can kill tumor cells, grown either in petri dishes or immune compromised mice. IDO inhibitors could not have been discovered this way, because they act indirectly to stimulate the immune system to do the killing."

Muller and Prendergast are enthusiastic about the new strategy for clinical treatment of other cancers in addition to breast cancer. "There is growing evidence that cancer cells elude detection by the immune system," Prendergast said. "Our findings suggest that by blocking IDO we can 'uncloak' cancer cells to the immune system in a way that will increase the efficiency of chemotherapeutic treatment(s)."

The Lankenau Institute for Medical Research is a hospital-based nonprofit research institute in suburban Philadelphia, PA. The Institute's mission is to improve human health and well being by uncovering causes and better treatments for cancer, heart disease, and other diseases of aging. A major focus of the Institute is to identify genetic risk factors for disease and to develop novel strategies for prevention and treatment of these diseases based on this information.

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