Blood vessels in a human colorectal cancer, Ehaar El-Emir, Wellcome Images

Inflammation and colon cancer

20 July 2015

Dr Kepeng Wang won a Croucher Foundation Fellowship in 2009 when he started his postdoctoral studies in cancer research at the Department of Pharmacology, University of California, San Diego.

Through his research, under the mentorship of world-renowned scientist in the field of inflammation and cancer, Professor Michael Karin, Wang discovered that colonic adenoma cells harbour defective mucin production and epithelial tight junctions. As a consequence, common microflora bacteria and their products are able to infiltrate the tumour microenvironment and trigger “tumuor-elicited inflammation”, which promotes the growth and progression of colorectal cancer.

Using a mouse model of colorectal cancer that closely mimics the process of human colonic tumuorigenesis, Wang and his colleagues used genetic tools to remove the two genes responsible for inflammation, to observe the change in rate of colon cancer progression. The work led to the discovery that interleukin-23 (IL-23)/IL-17 axis of inflammation strongly promotes colorectal cancer development. IL-17 and IL-23 inflammatory cytokines are important in protecting hosts against pathogen infections, but, in the case of colon cancer, serve as cancer driver by promoting the growth, survival and therapy resistance of cancer cells. Alongside his colleagues, Wang has had two major papers published in prestigious scientific journals, explaining observations on the role of inflammatory cytokines, IL-17 and interleukin-23 IL-23 on colon cancer: as a co-first author of “Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth”, Nature volume 490, issue 7423, November 2012; and as leading author of “Interleukin-17 receptor a signalling in transformed enterocytes promotes early colorectal tumourigenesis”, Immunity, volume 41, Issue 6, December 2014.

The current prognosis for colorectal cancer is poor – particularly in late stages. High expression of IL-23/IL-17 pathway genes is also associated with worse prognosis for human colorectal cancer patients. Targeting these inflammatory pathways may therefore improve current treatment scheme for colorectal cancer in humans. Through his research, Wang hopes to provide insight towards the development of new colon cancer therapies through the regulation of tumour infiltrating immune cells and the associated inflammation. Such treatment may prove effective for two reasons: firstly, inflammation drives cancer development; and secondly, unlike constantly mutating cancer cells, immune cells do not mutate, and therefore anti-inflammatory treatment may be effective for a long period compared to conventional anti-cancer approaches.

Dr Kepeng Wang received his PhD from the Hong Kong University of Science and Technology in 2008, under the supervision and mentorship of Professor Zhenguo Wu. His focus was on the role of JAK/STAT signaling in regulating the expansion and differentiation of skeletal muscle progenitor cells. During his PhD he worked on the role of inflammatory molecules controlling the behaviour of adult skeletal muscle progenitor cells. In 2009, following completion of his PhD he moved to the US to pursue postdoctoral research, with support from the Croucher Foundation.

To view Dr Kepeng Wang’s Croucher profile, please click here.

For more information about Croucher Fellowships, please click here.