Project Details

While the development of combination chemotherapy regimens and the approval of a number of biological agents has resulted in significantly improved response rates and prolonged survival in patients with metastatic colon cancer, the vast majority of patients eventually develop resistance to the these agents. As a result, 5 year survival rates for patients with inoperable metastatic colon cancer remains below 20%. Identification of the escape pathways induced by tumour cells in response to continued drug exposure may provide insight into alternative treatment strategies. Through continuous culture to increasing doses of chemotherapeutic drugs in vitro, we have generated colon cancer cell lines with acquired resistance to the major agents used in the treatment of colon cancer – 5FU, irinotecan and oxaliplatin. The advent of whole genome, transcriptome and proteome profiling technologies now offers an unprecedented opportunity to characterize these cell lines and delineate the pathways involved in acquired resistance. This PhD project will involve the continued development of these cell lines, their characterization using cutting edge technologies such as Next-generation sequencing, and the testing of rational treatment strategies to overcome the acquired resistance.

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