Identification of novel clinical response biomarkers in colorectal cancer

Colorectal cancer, one of the most common cancers in the UK, is treated by a multi-disciplinary team, combining expertise in surgery, chemotherapy and radiotherapy. Current treatment protocols do not, however, routinely consider individuality in factors including patient genotype, tumour gene expression and mutation burden, although we and others have shown that these can be significant determinants of both disease progression and treatment response.  Clinical response is additionally often limited by the development of drug or radiation resistant disease, although the molecular basis of this treatment-limiting complication is not well understood.

In collaboration with Tayside Tissue Bank, we have unique access to large, well-characterised cohorts of pre-malignant colorectal adenomas and colorectal tumours, using which we have identified key oncogenes, including K-Ras, individuality in the expression and activity of which significantly influences both disease progression and treatment response. We have recently used whole genome mRNA and microRNA profiling to further understand the molecular mechanisms contributing to individuality in response to chemotherapy and radiotherapy. We have developed novel experimental models and created novel drug resistant cell lines, further analysis of which will form the basis of this PhD project.

This clinically relevant translational PhD project will be supervised by an experienced collaborative research team, combining expertise in laboratory science, colorectal surgery, clinical oncology, pathology and clinical genetics, and will use a variety of experimental approaches to investigate the molecular basis of individuality in disease progression, chemotherapy and radiotherapy response in colorectal cancer.

References: Smith et al, Proc Natl Acad Sci USA 2002 99:9433-9438; Leslie et al, Cancer Res 2003 63: 4656-4661; Conlin et al, Gut 2005 54: 1283-1286; Smith et al, Br J Cancer 2011 102: 693-703; Weidlich et al, Br J Cancer 2011 105: 246-254

Other Requirements: Minimum of 2:1 degree in biological sciences or equivalent, IELTS English Language score of 6.5 overall (no component less than 6.0)

Dr Gillian Smith
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