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Revolutionary Eye Cancer Treatment

loped by Roche Pharmaceuticals (Nutley, N.J.) for a similar use against a related target called MDM2 in adult cancer cells.

The success in knocking out MDMX with nutlin-3 represents the first example of local delivery of a targeted chemotherapy drug for any childhood cancer, Dyer said.

Targeted therapy uses a customized drug to disable a specific molecule inside a growing cancer cell; local delivery is the placement of a drug at the site of disease, rather than systemic treatment. In systemic treatment, such as chemotherapy, a drug is infused into the body through a vein and then circulates, often causing toxic side effects that are especially challenging in children.

After demonstrating that nutlin-3 is effective when applied directly to the eye, the St. Jude team modified the treatment by combining this molecule 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.

"The findings suggest that this treatment not only could offer children with retinoblastoma more effective and less-toxic treatment," Dyer said. "It could also increase the chance that their vision can be preserved by eliminating the tumor and preventing its spread from the eye to the rest of the body."

The discovery that blocking MDMX releases the apoptosis response in retinoblastoma has important implications for certain forms of adult cancers as well. "Some forms of breast, lung, prostate and colon cancer are caused by abnormally large quantities of MDMX in the cells," Dyer explained. "So knocking out MDMX in those cancers might also dramatically reduce tumor size. And administering the drug directly to the site of the tumor could make the treatment especially effective while avoiding the toxicity caused by systemic exposure." T
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