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[2014/03/21] The NYMU-TVGH Colorectal Cancer Research Team Discovers the Mechanism for Cancer Stem Cells Expansion and Target Therapy Resistance

[2014/03/21]

The NYMU-TVGH Colorectal Cancer Research Team Discovers the Mechanism for Cancer Stem Cells Expansion and Target Therapy Resistance

The National Yang-Ming University-Taipei Veterans General Hospital (NYMU-TVGH) colorectal cancer research team recently discovers an important finding in colorectal cancer progression and therapeutic resistance. On 13th March, 2014, the group revealed their results in a press conference held in National Yang-Ming University.

Colorectal cancer includes cancers originate from colon and rectum. In recent years, the incidence of colorectal cancer in Taiwan increases and now it ranks as the third leading cause of cancer-related death in Taiwan. The major strategies for treating colorectal cancers include surgical resection for the early-stage disease, surgery combined with adjuvant chemotherapy for the lymph-node metastasis cases, and chemotherapy combined with molecular target agents for metastatic diseases. Targeting epidermal growth factor receptor (EGFR) is the main strategy for treating late-stage colorectal cancers, and KRAS status is a useful biomarker for selecting patients to receive anti-EGFR treatment. However, there are certain cases fail to respond to anti-EGFR treatment though carrying wild-type KRAS. The underlying mechanism and the strategy for KRAS-independent anti-EGFR resistance are unclear.

The NYMU-TVGH colorectal cancer research team is a multidisciplinary team composed of members with different specialties. The members include Dr. Hsei-Wei Wang, the professor of Institute of Microbiology and Immunology, is the expert of genomic science; Dr. Muh-Hwa Yang, the professor of Institute of Clinical Medicine of National Yang-Ming University and also the attending physician of Division of Hematology-Oncology of Taipei Veterans General Hospital, is the expert of cancer biology and medical oncology; Dr. Jeng-Kae Jiang, the director of Division of Colorectal Surgery of Taipei Veterans General Hospital, is the expert of colorectal surgery; and Dr. Wei-Lun Hwang, the postdoctoral researcher of Institute of Microbiology and Immunology of National Yang-Ming University. They performed a series of cell biology and molecular biology experiments to prove the concept that in colorectal cancer stem cells, the transcriptional factor Snail induces the expression of microRNA-146a to direct the symmetrical expansion of cancer stem cells. The expansion of colorectal cancer stem cells genders resistance to anti-EGFR agent. Intercepting this signal by the MEK or Beta-catenin inhibitors sensitizes the colorectal cancer stem cells to the anti-EGFR agent. The results were confirmed by animal experiments and importantly, in human colorectal cancer samples from KRAS wild-type, anti-EGFR agent-treated cases.

Dr. Wang and Dr. Yang explained that this finding is valuable in both scientific and clinical aspects. Scientifically, they identified the molecular mechanism of cancer stem cells expansion in colorectal cancers. Clinically, the result provides the important information for the future development of strategies to reverse anti-EGFR resistance in late-stage patients. This major finding has been published in the 2014 March issue of Nature Cell Biology and is highlighted in the News and Views in the same issue.

President Liang and NYMU-TVGH colorectal cancer research team in the press conference

President Liang(left 3) and NYMU-TVGH colorectal cancer research team in the press conference


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