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Research points to why some colorectal cancers recur after treatment

Study sheds new light on monoclonal antibody therapy cetuximab

Date:
November 16, 2015
Source:
University of Texas M. D. Anderson Cancer Center
Summary:
Cetuximab, marketed as Erbitux, is one of the key therapies for metastatic colorectal cancer. Yet the cancer still returns in some patients, shortening overall survival. New research reveals insight into how key proteins, known as epidermal growth factor receptors (EGFR), are regulated, leading to resistance.
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Cetuximab, marketed as Erbitux®, is one of the key therapies for metastatic colorectal cancer. Yet the cancer still returns in some patients, shortening overall survival.

A study at The University of Texas MD Anderson Cancer Center may help explain why the body sometimes becomes resistant to this therapy. The results, published in the Nov. 16 online issue of the Journal of Clinical Investigation reveal new insight into how key proteins, known as epidermal growth factor receptors (EGFR), are regulated, leading to resistance.

"Our study investigated the role of extracellular methylation in EGFR signaling, and unexpectedly discovered new information about how EGFR renders cancer cells resistant to cetuximab antibody therapy," said Mien Chie Hung, Ph.D., chair of Molecular and Cellular Oncology.

Methylation is a process by which proteins are chemically altered. EGFR, when expressed aberrantly, can lead to cellular changes including runaway cell growth, reduced cell death, tumor formation and metastasis. Hung's group found that expression of methylation-defective EGFR reduced tumor growth in mice.

"More importantly, we showed that increased methylation of EGFR resulted in resistance to cetuximab mediated cancer cell growth," said Hung. "This correlated with poorer clinical outcomes observed in colorectal cancer patients and higher recurrence rates following cetuximab treatment."

The study showed that EGFR methylation was mediated by PRMT1, a protein involved in a variety of genetic processes including gene transcription, DNA repair and signaling.

"EGFR methylation sustained signaling activity and cell proliferation even in the presence of cetuximab," said Hung. "This data suggests that this specific methylation plays an important role in regulating EGFR functionality and resistance to cetuximab treatment."


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Materials provided by University of Texas M. D. Anderson Cancer Center. Note: Content may be edited for style and length.


Journal Reference:

  1. Hsin-Wei Liao, Jung-Mao Hsu, Weiya Xia, Hung-Ling Wang, Ying-Nai Wang, Wei-Chao Chang, Stefan T. Arold, Chao-Kai Chou, Pei-Hsiang Tsou, Hirohito Yamaguchi, Yueh-Fu Fang, Hong-Jen Lee, Heng-Huan Lee, Shyh-Kuan Tai, Mhu-Hwa Yang, Maria P. Morelli, Malabika Sen, John E. Ladbury, Chung-Hsuan Chen, Jennifer R. Grandis, Scott Kopetz, Mien-Chie Hung. PRMT1-mediated methylation of the EGF receptor regulates signaling and cetuximab response. Journal of Clinical Investigation, 2015; DOI: 10.1172/JCI82826

Cite This Page:

University of Texas M. D. Anderson Cancer Center. "Research points to why some colorectal cancers recur after treatment: Study sheds new light on monoclonal antibody therapy cetuximab." ScienceDaily. ScienceDaily, 16 November 2015. <www.sciencedaily.com/releases/2015/11/151116181208.htm>.
University of Texas M. D. Anderson Cancer Center. (2015, November 16). Research points to why some colorectal cancers recur after treatment: Study sheds new light on monoclonal antibody therapy cetuximab. ScienceDaily. Retrieved May 23, 2017 from www.sciencedaily.com/releases/2015/11/151116181208.htm
University of Texas M. D. Anderson Cancer Center. "Research points to why some colorectal cancers recur after treatment: Study sheds new light on monoclonal antibody therapy cetuximab." ScienceDaily. www.sciencedaily.com/releases/2015/11/151116181208.htm (accessed May 23, 2017).

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