Inflammatory pathway spurs cancer stem cells to resist HER2-targeted breast cancer treatment

Public release date: 19-Jul-2012 [ | E-mail | Share ]

Contact: Nicole Fawcett nfawcett@umich.edu 734-764-2220 University of Michigan Health System

ANN ARBOR, Mich. Breast cancer treatments such as Herceptin that target a marker called HER2 have dramatically improved outcomes for women with this type of cancer. But nearly half of these cancers are resistant to Herceptin from the start and almost all of them will eventually become resistant.

Now, researchers at the University of Michigan Comprehensive Cancer Center have discovered one reason why the cancer cells become resistant: They turn on a completely different pathway, one that is involved in inflammation, fueling the cancer independently of HER2.

The pathway at work involves a protein called Interleukin-6, or IL-6. The researchers also showed in mice that a drug that blocks IL-6 can stop this effect and overcome the Herceptin resistance.

"Resistance to HER2-targeted therapies remains a major challenge in treating breast cancer. Our study suggests that an IL-6 inhibitor in combination with Herceptin may be a valuable addition for treating HER2-positive breast cancer," says senior study author Max S. Wicha, M.D., Distinguished Professor of Oncology and director of the U-M Comprehensive Cancer Center.

Results of the study will be published in the Aug. 24 issue of Molecular Cell.

Not only are these cells resistant to Herceptin, but they develop higher proportions of cancer stem cells, the small number of cells within a tumor that fuel the growth and spread. This makes the tumor extremely aggressive and likely to spread throughout the body. The IL-6 inhibitor also was shown to prevent this increase in cancer stem cells.

"There is evidence that patients with a lot of IL-6 tend to do poorly. What we found now is that in many of the Herceptin-resistant breast cancers, the IL-6 inflammation loop is driving the cancer stem cell," says lead study author Hasan Korkaya, D.V.M., Ph.D., research assistant professor of internal medicine at the U-M Medical School.

The researchers found that blocking the IL-6 inflammatory loop almost completely blocked the cancer and the stem cells. Mice treated with the IL-6 blocker along with Herceptin immediately after the cancer developed never became resistant to Herceptin.

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Inflammatory pathway spurs cancer stem cells to resist HER2-targeted breast cancer treatment