Blocking Inflammation Receptor Kills Breast Cancer Stem Cells, Study Finds

ScienceDaily, January 4, 2010

The relationship between inflammation and cancer has always been suspected. Especially in breast cancer where infiltration of inflammatory macrophages into the tumor has historically been associated with poor survival. Recently investigators at the University of Michigan Comprehensive Cancer Center have reported new evidence that inflammation and breast cancer may be linked, specifically studying the breast cancer stem cells.

In a study published in the January 4th issue of the Journal of Clinical Investigations, researchers identified a receptor, CXCR1, on the cancer stem cells which triggers growth of stem cells in response to inflammation and tissue damage. A drug originally developed to prevent organ transplant rejection blocks this receptor, killing breast cancer stem cells and preventing their metastasis in mice, according to the study. CXCR1 is the receptor for an inflammatory cytokine called interleukin-8, which is found in numerous conditions, produced by macrophages and inflamed fibroblasts. The interesting point about the current research is that breast cancer cells are conventionally seen as being resistant to treatment approaches commonly used such as chemotherapy or radiotherapy. The reason for this is that tumor stem cells are not associated with high rates of multiplication, rather they are "sleeping" in the tumor, being ready to make new tumors once the main mass of the tumor is destroyed.

"Developing treatments to effectively target the cancer stem cell population is essential for improving outcomes. This work suggests a new strategy to target cancer stem cells that can be readily translated into the clinic," says senior study author Max S. Wicha, M.D., Distinguished Professor of Oncology and director of the U-M Comprehensive Cancer Center. Wicha was part of the team that first identified stem cells in breast cancer. According to the disclosures section of the press release, the University of Michigan has filed for patent protection on this technology, and is currently looking for a commercialization partner to help bring the technology to market.

In the study, investigators demonstrated that the anti-organ rejection drug repertaxin alone, or when combined with classical chemotherapies, was capable of reducing the number of tumor stem cells, as well as suppressing ability of the tumors to develop metastases.

"These studies suggest that important links between inflammation, tissue damage and breast cancer may be mediated by cancer stem cells. Furthermore, anti-inflammatory drugs such as repertaxin may provide a means of blocking these interactions, thereby targeting breast cancer stem cells," Wicha says.

There are several companies working on targeting tumor stem cells, these include OncoMed, which is currently developing antibodies targeting tumor stem cells, and ImmunoCellular Therapeutics, which are targeting tumor CD133 expressing stem cells. To our knowledge, no clinical trials have initiated based on approaches targeting tumor stem cells, however several of these are planned.