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SWCRF Researcher Identifies Ways to Significantly Expand the Applicability of a Unique Anti-Cancer Drug

Wilson H. Miller, Jr.
Professor – Department of Medicine
Division of Experimental Medicine
McGill University

NEW YORK, July 22, 2008--Arsenic Trioxide is a drug with an amazing impact on reversing the growth of acute promyelocytic leukemia (APL) cells, as earlier SWCRF-funded research proved.  The drug works through a mechanism which is not fully understood, but is known to be different from that of any other cancer-fighting drug.  This unique mechanism gives the compound tremendous potential impact as a way to overcome resistance developed by cancer over time to whole categories of anti-cancer drugs. 

Dr. Miller’s research has identified how arsenic trioxide can be used in combination with other cancer-fighting drugs to significantly increase the overall anti-cancer effect.  Arsenic trioxide-based combination therapy has already shown promise in non-APL acute myelogenous leukemia and multiple myeloma, and Dr. Miller’s research opens the possibility of addressing the challenges of Herceptin-resistant breast cancer and a variety of other devastating cancers.

Recent research has made tremendous strides in understanding the molecular signals that tell cells how to behave.  Some of these signals promote a cell’s growth and some the cell’s death.  Not surprisingly, arsenic trioxide promotes signals leading to death of cancer cells. Dr. Miller’s research has identified several specific signaling pathways that would permit two strategies to take advantage of arsenic trioxide’s unique mechanism by creating combination drug treatments with a more powerful impact on cancer cells:
the arsenic reduces a growth-producing signal to enhance the effectiveness of another drug that targets that signaling pathway or
another drug clears the way for arsenic trioxide to more effectively kill cancer cells.
Arsenic treatment targets destruction of a growth dependent signal called AKT needed in large amounts in many forms of cancer, including breast cancer. As a result, arsenic, when combined in clinical trials with other drugs such as HSP 90 inhibitors (which were discovered by Neal Rosen, another SWCRF-supported scientist), can effectively target cancer cells while minimally affecting normal cells.   This combination might address the challenges of Herceptin-resistant breast cancer and a variety of other devastating cancers.

Koren K. Mann, Myrian Colombo, and Wilson H. Miller, Jr. Arsenic trioxide decreases AKT protein in a caspase-dependent manner Mol Cancer Ther Mann et al. 7 (6): 1680. 


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Posted: July 2008