Chemotherapeutic drugs, 5-fluorouracil and cisplatin, differentially affect exprssion of drug metabolising enzyme genes in an oesophageal cancer cell line

Master Thesis

2014

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University of Cape Town

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Cancer is a leading cause of death worldwide. Oesophageal cancer in particular is the sixth most common cause of cancer deaths globally and its incidence and mortality rates in Southern Africa are among the highest in the world. One of the major challenges with cancer treatment is the vast variability in patient response to chemotherapy, which is predominantly due to genetic variability. The most relevant genes in this context encode the CYP and GST drug metabolising enzymes (DMEs) as these enzymes metabolise up to 90% of clinically-prescribed medication. Patients are also exposed to a variety of other compounds that along with chemotherapeutic drugs may alter DME gene expression. Changes in DME gene expression influence the therapeutic outcomes for patients; thus, understanding the effects of drugs and compounds on the expression of DMEs is crucial for the advancement of personalised medicine. The aim of this study was to determine the effects of two commonly-used chemotherapeutic drugs, as well as a CYP-inducing compound, on the differential expression of four pharmacogenetically relevant DME-encoding genes, CYP1A1, 1A2, 1B1 and GSTP1, in a human oesophageal cancer cell line.
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