Clinical and translational aspects of colorectal cancer

Clinical research

The focus of clinical colorectal cancer research is in two areas; new endoscopic polyp detection techniques and advanced endoscopic polyp resection techniques.

Polyp detection – Fluorescent molecular imaging endoscopy in the colon

Together with Edinburgh Molecular imaging, The Centre for Human Drug research and Groningen University Medical Centre we are investigating the use of a fluorescent tracer to detect colorectal polyps in patients. We hope to detect more polyps by using a fluorescence endoscope to detect the tracer that binds specifically to a protein (cMet) on the surface of polyp and cancer cells, making polyps and cancers fluoresce.

Polyp resection – Endoscopic Submucosal Dissection

Endoscopic Submucosal Dissection is a technically demanding technique whereby large polyps and early cancers can be removed in one piece endoscopically without surgery. We are performing clinical trials of this technique to compare it with transanal surgery and Endoscopic Mucosal Resection (EMR).

 

Translational research

The BMP pathway in colorectal cancer invasion and metastasis

The focus of our translational research is the role of the Bone Morphogenetic Protein pathway in colorectal cancer. The last few years we have been focussing on the role of this pathway in the tumour/stroma interaction where cancer cells and surrounding non-cancer cells come into contact and influence each other.

The use of Statins for colorectal cancer prevention

We have also continued to explore the potential use of cholesterol lowering drugs (Statins) to prevent colorectal cancer and the mechanisms by which they may do this.

 

Biosketch

James Hardwick received his initial training in gastroenterology and general internal medicine in the UK. In 1999 he moved to Amsterdam where he was awarded a PhD with the thesis entitled “Molecular Mechanisms in Colon Cancer” on 25 September 2002. His research interests include the molecular biology of colorectal cancer initiation and progression and new endoscopic techniques for the detection and removal of neoplastic lesions in the colon. His clinical interests are colorectal cancer screening, Endoscopic Mucosal Resection and Endscopic Submucosal Dissection of advanced intestinal neoplasia. In 2007 he moved from the Academic Medical Centre in Amsterdam to the Leiden University Medical Centre where he was appointed Professor of Gastroenterology in 2014 holding his inaugural lecture entitled “Colon Cancer through the looking glass” on 18 September 2015.

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Selected publications

Burggraaf, J., Kamerling, I.M.C., Gordon, P.B., Schrier, L., de Kam, M.L., Kales, A.J., Bendiksen, R., Indrevoll, B., Bjerke, R.M., Moestue, S.A., Yazdanfar, S., Langers, A.M.J., Swaerd-Nordmo, M., Torheim, G., Warren, M.V., Morreau, H., Voorneveld, P.W., Buckle, T., van Leeuwen, F.W.B., Odegardstuen, L.I., Dalsgaard, G.T., Healey, A. & Hardwick, J.C.H. Detection of colorectal polyps in humans using an intravenously administered fluorescent peptide targeted against c-Met. Nature Medicine 21, 955-961 (2015).

Voorneveld, P.W., Reimers, M.S., Bastiaannet, E., Jacobs, R.J., van Eijk, R., Zanders, M.M.J., Herings, R.M.C., van Herk-Sukel, M.P.P., Kodach, L.L., van Wezel, T., Kuppen, P.J.K., Morreau, H., van de Velde, C.J.H., Hardwick, J.C.H. & Liefers, G.J. Statin Use After Diagnosis of Colon Cancer and Patient Survival. Gastroenterology 153, 470-479 e474 (2017).

Voorneveld, P.W., Kodach, L.L., Jacobs, R.J., Liv, N., Zonnevylle, A.C., Hoogenboom, J.P., Biemond, I., Verspaget, H.W., Hommes, D.W., de Rooij, K., van Noesel, C.J., Morreau, H., van Wezel, T., Offerhaus, G.J., van den Brink, G.R., Peppelenbosch, M.P., Ten Dijke, P. & Hardwick, J.C. Loss of SMAD4 alters BMP signaling to promote colorectal cancer cell metastasis via activation of Rho and ROCK. Gastroenterology 147, 196-208 e113 (2014).

Hardwick, J.C., Kodach, L.L., Offerhaus, G.J. & van den Brink, G.R. Bone morphogenetic protein signalling in colorectal cancer. Nat Rev Cancer 8, 806-812 (2008).

Barendse, R.M., Musters, G.D., de Graaf, E.J.R., van den Broek, F.J.C., Consten, E.C.J., Doornebosch, P.G., Hardwick, J.C., de Hingh, I., Hoff, C., Jansen, J.M., van Milligen de Wit, A.W.M., van der Schelling, G.P., Schoon, E.J., Schwartz, M.P., Weusten, B., Dijkgraaf, M.G., Fockens, P., Bemelman, W.A., Dekker, E. & group, T.S. Randomised controlled trial of transanal endoscopic microsurgery versus endoscopic mucosal resection for large rectal adenomas (TREND Study). Gut (2017).