Mr Simon Buczacki
Despite significant advances over the last decade in the adjuvant and neo-adjuvant treatment of colorectal cancer (CRC) disease relapse is not un-common. In laboratory settings chemotherapy is often highly efficacious although this clearly fails to translate in completeness to the clinic. One modern explanation for this proposes that highly tumorigenic cancer stem cells (CSCs) drive tumour growth and propagation employing unique strategies that lead to inherent resistance to adjuvant therapies. This CSC phenotype is contextual, plastic and governed by microenviromental/niche signalling cues rather than being fixed. Recent data points to a quiescent sub-set of CSCs that become clongenically active during adjuvant treatment. The aim of our research is to manipulate quiescent CSC niche signals through the use of biological therapies to alter the behaviour of quiescent CSCs, thereby increasing their susceptibility to conventional adjuvant cytotoxic therapy. We are using an in vitro 3D tumour spheroid drug screen to identify candidate molecules which we are then validating using in vivo lineage tracing and xenotransplant assays.
Nature. 2013. Mar 7;495(7439):65-9. Article. Intestinal label-retaining cells are secretory precursors expressing Lgr5. Buczacki SJA, Ireland Zecchini H, Nicholson AM, Russell R, Vermeulen L, Kemp R, Winton DJ. Science. 2013 Nov 22;342(6161):995-8. Defining stem cell dynamics in models of intestinal tumour initiation. Vermeulen L, Morrissey E, van der Heijden M, Nicholson A, Sottoriva A, Buczacki S, Kemp R, Tavaré S, Winton DJ British Journal of Cancer. 2011 Oct 25;105(9):1253-9. Stem cells, quiescence and rectal carcinoma: an unexplored relationship and potential therapeutic target. Buczacki S, Davies RJ, Winton DJ. Colorectal Disease. 2014. May;16(5):329-31. The confounding effects of tumour heterogeneity and cellular plasticity on personalised surgical management of colorectal cancer. Buczacki SJA, Davies RJ.