Publications by authors named "Lesley Jardine"
Background: Glucuronidation represents a novel mechanism of intrinsic drug resistance in colon cancer cells. To safely reverse this mechanism in vivo, it is essential to identify which isoforms of UDP-glucuronosyltransferases are responsible for catalysing this drug metabolism in tumour tissue.
Materials And Methods: LC-MS was applied to measure rates of glucuronidation of two anticancer compounds (SN-38 and NU/ICRF 505) by patient colon cancer biopsies and paired normal colon.
Article Synopsis
- Colon cancer is resistant to chemotherapy due to mechanisms like glucuronidation, which involves the enzyme UDP-glucuronosyltransferases (UGTs).
- Research identified UGT1A9 as the key enzyme in glucuronidating two topoisomerase I inhibitors, enhancing drug resistance in colon cancer cells.
- Inhibiting this glucuronidation can significantly increase drug effectiveness, suggesting that dietary substances and certain medications could potentially alter drug resistance in colon cancer.
Often the use of cytotoxic drugs in cancer therapy results in stable disease rather than regression of the tumor, and this is typically seen as a failure of treatment. We now show that DNA damage is able to induce senescence in tumor cells expressing wild-type p53. We also show that cytotoxics are capable of inducing senescence in tumor tissue in vivo.
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