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Researchers uncover a viable way for colorectal cancer patients to overcome drug resistance
Date:4/4/2012

CHICAGO, IL (April 4, 2012)When combined with other treatments, the drug cetuximabwhich works by slowing or stopping the growth of cancer cellshas been shown to extend survival in certain types of cancer, including metastatic colorectal cancers. Unfortunately, about 40 percent of colorectal cancer patientsspecifically those who carry a mutated form of a gene called KRASdo not respond to the drug. Researchers at Fox Chase Cancer Center in Philadelphia, however, have been working on a way to overcome this resistance to cetuximab by unleashing a second cetuximab driven mechanism using a novel drug called ARI-4175. The researchers from Fox Chase will present their findings at the AACR Annual Meeting 2012 on Wednesday, April 4.

In mice that had KRAS mutated colorectal cancer, researchers found that ARI-4175 not only blocked tumor growth when used alone, but also when used in combination with cetuximab. They hypothesize that the new drug may work by enlisting "natural killer" cells of the body's own immune system to reject the tumor.

"We've discovered that ARI-4175 appears to increase the level of natural killer cells that could play a role in rejecting the tumor," Hossein Borghaei, D.O., director of thoracic medical oncology at Fox Chase and lead author on the study says. He notes that this actionrallying the body's own immunologic defensesmay explain why ARI-4175 effectively stops the growth of tumors. "My theory is that this particular drug turns on the host's anticancer immune response, while cetuximab serves to help direct it toward the cancer."

Borghaei, along William W. Bachovchin, Ph.D., professor of biochemistry at Tufts Sackler School of Graduate Biomedical Sciences (also co-author on the study) and colleagues, tested ARI-4175 in colorectal cancer cell lines and in mice with two types of cetuximab-resistant colorectal tumors. Neither cetuximab nor ARI-4175, separately or together, succeeded in killing the cells in lab dishe
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Contact: Diana Quattrone
Diana.Quattrone@fccc.edu
215-815-7828
Fox Chase Cancer Center
Source:Eurekalert

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