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Old 03-26-2005, 01:59 PM   #1
Roxi1
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Type of Breast Cancer Metastasis Studied
Discovery Leads to Drug Development

Researchers have solved the mystery of why an aggressive form of HER2-positive breast cancer travels readily to lungs, liver and bone, where it then establishes new tumors. The finding may lead to strategies that block the deadly spread.

In a study funded by the National Institutes of Health, the National Breast Cancer Research Foundation and the U.S. Army Breast Cancer Research Program, M. D. Anderson scientists discovered a lethal attraction between signals found on HER2-positive breast cancer cells and those on the surface of targeted organs.

It explains why this form of breast cancer, which affects up to 30% of patients, can be so invasive. The vast majority of women who die from breast cancer develop secondary tumors in their lungs, liver and bones.

Chemical attraction links proteins

"It has always been a puzzle as to why, when HER2-positive cancer cells circulate throughout the body, they preferentially travel to these organs," says the study's lead author, Mien-Chie Hung, Ph.D., a professor and chair of M. D. Anderson’s Department of Molecular and Cellular Oncology. "We now have explained it biochemically and hope that this leads to strategies that prevent such metastasis."

The discovery focuses on the relationship between HER2 and chemokine receptor proteins on breast cancer cells. Chemokines are a large family of proteins that initiate an inflammatory response, which attracts them to circulating white blood cells that have a corresponding receptor. Researchers have found that some diseases, including HIV and cancer, use this same chemical attraction to invade the body.

Although scientists already had discovered that the chemokine receptor CXCR4 was involved in the tendency of certain breast cancers to target other organs, they did not know how CXCR4 did that for HER2-postive breast cancer until now.

HER2 intensifies chemical attraction

HER2-positive breast cancer cells that float free of the tumor are studded with excess CXCR4 receptors, which are previously known to be attracted to another chemokines produced by the target organs. This strong attraction causes HER2-positive breast cancer cells to leave the blood and lymphatic systems and migrate to organs with large amounts of these chemokines, where they settle and grow.

"HER2 turns on and then magnifies the ability of these cancer cells to zero in on organs that release this chemical signal," Hung says. "That explains why HER2 breast cancers can so easily induce metastasis."

Examining human breast tumor tissues, researchers found a significant correlation between HER2 and CXCR4, and also observed that the presence of CXCR4 was associated with a poor overall survival rate in patients with breast cancer.

Discovery leads to drug development

In lab and animal studies, Hung and his group then showed that when they blocked CXCR4 in tumors by using a special RNA molecule, the cancer became less invasive.

The discovery may help physicians predict where HER2-positive breast cancer will metastasize. The finding also "provides strong support for the notion that an agent that can block CXCR4 could have anticancer potential," Hung says. Efforts are now under way to develop such a drug to treat cancer, he adds.
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Old 03-30-2005, 05:04 AM   #2
Christine MH
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Hi Roxi1,

Your article made me wonder whether there were any other known CXCR4 antagonists out there. Did a quick search through Pubmed and its seems as though CXCR4 plays a role in alot of diseases, including MS and some AIDS (including the really bad one that was discovered in New York), so there is alot of work going on in this area and even one antagonist that has made it into human trials, (http://www.ncbi.nlm.nih.gov/entrez/q..._uids=15752146). One of the articles linked CXCR5 to central nervous system mets in BC and it would be great to have something that blocked those.
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