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Preclinical data support ongoing clinical trials testing IDO inhibitors as a treatment for cancer
Date:7/19/2012

PHILADELPHIA Inhibitors of indoleamine 2,3-dioxygenase (IDO) are being assessed in clinical trials as a potential treatment for recurrent or refractory solid tumors. Clear genetic rationale for these trials, together with evidence that primary and metastatic lung tumors might be particularly susceptible to the drugs, is now reported in a preclinical study published in Cancer Discovery, a journal of the American Association for Cancer Research.

"Our data provide preclinical genetic validation for the ongoing clinical trials testing IDO inhibitors in cancer patients," said Alexander Muller, Ph.D., associate professor at Lankenau Institute for Medical Research in Wynnewood, Pa. "We also believe that our results indicate that these drugs could have particular impact in patients with lung adenocarcinoma and lung metastases, conditions for which there is an urgent, unmet need for new therapeutic options."

The ongoing clinical trials were initiated based on pharmacological studies that indicated that IDO inhibitors can enhance the effectiveness of other therapies in mouse models of cancer. Genetic evidence to support the concept was lacking. Muller and his colleagues, therefore, set out to determine the effect of disrupting the IDO gene on tumor development in mice.

"It was very important to us to use models of disease as physiologically relevant as possible," he said. "We chose the KRAS-induced lung carcinoma model as our model of primary disease since tumors can be induced selectively in the lung and are driven by mutations in a gene known to be affected in approximately 20 percent of nonsmall cell lung cancers. We modeled metastatic disease using the 4T1 mouse breast cancer cell line, which very efficiently metastasizes to the lung after being engrafted in the mammary glands of mice. This is one of only a few breast cancer models with the capacity to metastasize efficiently to sites affected in human breast cancer patients."


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Contact: Jeremy Moore
Jeremy.Moore@aacr.org
215-446-7109
American Association for Cancer Research
Source:Eurekalert

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