Differentiation and drug responses in colorectal cancer
Derangement of cellular differentiation is a key step in the progression of all carcinomas. Understanding the molecular basis of differentiation and its derangement in cancers should provide novel targets for the development of new treatments, and new approaches to diagnosis and early detection
We use a large extensively characterised panel of more than 100 colorectal cancer (CRC) derived cell lines, together with newly derived organoid cultures from primary CRCs, for in vitro studies of the control of differentiation. We also use patient derived myofibroblast cell lines in co-culture with the CRC cell lines to mimic the epithelial microenvironment.
With these resources, we have developed a system for analysing differentiation within our panel of CRC derived cell lines.
Our goal is to define the molecular pathways of differentiation control more clearly than has been possible so far, and so enable a finer classification of CRCs through identification of the particular gene functions that are altered in any given cancer.
This should suggest novel targets for drug development and provide the basis for a finer preclinical analysis of drug responses. Our focus is on immune mediated responses to monoclonal antibody derived mono- and combination therapies.