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    Michael A. Dyer, PhD

    Michael A. Dyer, PhD

    St. Jude announces breakthrough in eye cancer treatment

    Scientists at St. Jude Children's Research Hospital have demonstrated in the laboratory a new, locally applied treatment for the eye cancer retinoblastoma that not only greatly reduces the size of the tumor, but does so without causing the side effects common with standard chemotherapy. In addition, this treatment shows promise for fighting certain forms of breast, lung, prostate and colon cancer, and it could be used to help children in poorer nations of the world. According to researchers, this is the first example of local delivery of a targeted chemotherapy drug for any childhood cancer.

    A report on this work appears in the Nov. 2 issue of the journal Nature. Retinoblastoma occurs in about 300 children in the United States every year (in comparison, breast cancer strikes some 200,000 women). It is always lethal if not treated.

    This breakthrough is based on an earlier discovery at St. Jude that overturned a widely held belief about the process of apoptosis, or cell suicide, in retinoblastoma, according to Michael Dyer, Ph.D. He is a Pew Scholar and associate member of the St. Jude Department of Developmental Neurobiology. Apoptosis is the way the body rids itself of abnormal cells that might become cancerous.

    Until now, retinoblastoma experts thought that a mechanism called the p53 pathway triggered apoptosis in other types of cancer cells but not in retinoblastoma. But the St. Jude team not only proved that the pathway was activated in early-stage retinoblastoma, but that excessive levels of a molecule called MDMX blocked it from triggering apoptosis in more advanced tumors. Based on this discovery, the St. Jude team used a molecule called nutlin-3 to block MDMX in retinoblastoma cells in the laboratory. This likely means that retinoblastoma eventually can be treated locally and easily without the prospect of losing the eye.

    After demonstrating the effectiveness of locally applied nutlin-3, the team combined it with topotecan, a drug also being investigated in the treatment of retinoblastoma. Local delivery of this two-drug targeted treatment was even more effective, reducing tumor size significantly more than the most effective known combination of standard chemotherapy drugs.

    “Our finding with locally applied nutlin-3 also has major implications for certain forms of adult cancers, since some forms of breast, lung, prostate and colon cancer are caused by abnormally large quantities of MDMX,” Dyer explained. “So knocking out MDMX in those cancers might also dramatically reduce tumor size.”

    Finding a way to deliver the drug directly to the tumor would eliminate the need for chemotherapy that affects the entire body with toxicity and violently unpleasant side effects. St. Jude researchers now are studying ways in which that could be accomplished, such as by sending tiny “bubbles” of chemotherapy drugs into the bloodstream; these drugs would travel only to the tumor location. Additional research is now being done to prepare for clinical trials in the future.

    This work also holds hope for children in poorer nations. A simple, localized treatment for retinoblastoma could be administered by local eye doctors, saving thousands of children who die in undeveloped countries each year—or lose their sight—because they do not have access to hospital care.

    November 2006