Targeting Chemokine Signaling to Overcome Radiation Resistance in Colorectal Cancer

An article published in Experimental Biology and Medicine (Volume 242, Issue 4, February, 2017) identifies a new pathway that renders colon cancers resistant to radiation therapy. The study, led by Dr. Zhuoxin Cheng, from the First Affiliated Hospitals of Harbin Medical University and Jiamusi University in China, reports that activation of CXCR4, a chemokine receptor, protects colorectal cancer cells from radiation-induced cell death.   

According to the American Cancer Society, colorectal cancer is the second leading cause of cancer-related deaths in the United States.  The current standard of care for patients with colorectal cancer includes surgical resection, chemotherapy and radiation therapy. Even though the initial response to therapy can be impressive, many patients experience relapses and even death because the tumor becomes resistant to radiotherapy.   Clinical outcomes for patients can be improved if the mechanisms that underlie colorectal cancer cell resistance to radiotherapy can be identified and inhibited.  

CXCL12, or stromal cell-derived factor 1, is a chemokine protein that is produced by many cells and activates the CXCR4 receptor.  Studies from other groups have demonstrated that the CXCL12-CXCR4 pathway is activated in many cancers and contributes to tumor initiation and growth. In the current study, Dr. Cheng and colleagues examined the contribution of the CXCL12-CXCR4 pathway to colorectal cancer cell radio-sensitivity.  Activation of this pathway attenuated the response of colorectal cancer cells to radiotherapy, and reduced the activity of proteins that induce cell death (BAX, caspase-3 and caspase-9). In contrast, inhibition of the pathway augmented the response to radiotherapy and decreased the expression of survival factors (survivin). These findings support inhibition of CXCL12-CXCR4 signaling as a therapeutic strategy for overcoming radiotherapy resistance in colorectal cancer.

Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine, said, “Cheng and colleagues provide a mechanism for the radiation resistance of colorectal cancer cells. This may provide future therapeutic targets that would improve the efficacy of radiation therapy for  treatment of colorectal cancer.”

About Experimental Biology and Medicine

Experimental Biology and Medicine is a journal dedicated to the publication of multidisciplinary and interdisciplinary research in the biomedical sciences. The journal was first established in 1903. Experimental Biology and Medicine is the journal of the Society of Experimental Biology and Medicine. To learn about the benefits of society membership visit www.sebm.org. If you are interested in publishing in the journal, please visit http://ebm.sagepub.com/.

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Source: Experimental Biology and Medicine