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Gleevec-resistant tumors respond to antibody treatment in mice

Conventional chemotherapy targets rapidly dividing cells in an effort to block cancer's growth. But many other cells in the body are also vulnerable to the often-harsh treatment. For the past few years, researchers and physicians have begun to pin their hopes on other types of therapies that specifically target cancer cells.

One such therapy is a small molecule called imatinib, also known as Gleevec, that recognizes and binds to certain receptors on the surface of some cancer cells. Originally developed for the treatment of leukemia, Gleevec was approved in 2002 for the treatment of another kind of cancer: gastrointestinal stromal tumors (GIST). And, for a while, it seemed to work miracles for people with advanced disease by blocking the activity of a receptor called KIT. But there was a hitch.

From our release:

"Gleevec, or imatinib, marked a paradigm shift in our understanding about cancer treatment and sparked much additional research into these inhibitors,” said Matt van de Rijn, MD, PhD, professor of pathology. “However, a new mutation almost always occurs over time in KIT that renders the tumor insensitive to the drug. We’ve found that treatment of these resistant cells with an antibody targeting KIT slows the growth of human GIST cells in cell culture and in animals, and increases their chances of being removed by the immune system."

The researchers believe it may be possible that the anti-KIT antibody treatment could be used as an alternative to, or even in combination with, imatinib or other small-molecule or antibody-based therapies to provide better control of the cancer.

The study, which was published online today in the Proceedings of the National Academy of Sciences, may offer a glimmer of hope for people with GIST and their family members.

van de Rijn collaborated with fellow pathologist Irving Weissman, MD, who directs Stanford's Institute for Stem Cell Biology and Regenerative Medicine, to conduct the research. The scientists hope to begin clinical trials in humans within the next couple of years.

Photo courtesy of Matt van de Rijn

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