Thymidylate synthase gene variations: predictive and prognostic markers
| Autor: | Georg Lurje, Philipp C. Manegold, Wu Zhang, A. Pohl, Heinz-Josef Lenz, Yan Ning |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
Antimetabolites Antineoplastic Colorectal cancer medicine.medical_treatment Biology Bioinformatics Thymidylate synthase Efficacy Genotype medicine Biomarkers Tumor Humans Chemotherapy Polymorphism Genetic Thymidylate Synthase medicine.disease Prognosis Chemotherapy regimen Gene Expression Regulation Neoplastic Oncology Pharmacogenetics Pharmacogenomics biology.protein Fluorouracil Colorectal Neoplasms |
| Zdroj: | Molecular cancer therapeutics. 8(5) |
| ISSN: | 1538-8514 |
| Popis: | Since its introduction more than 50 years ago by Heidelberger et al., the fluoropyrimidine 5-fluorouracil (5-FU) has remained the mainstay of therapeutic regimens used in the treatment of colorectal cancer and other human malignancies, with single-agent response rates of 20% to 25% in advanced disease stage. Pharmacogenomics has emerged as a useful tool to address interindividual gene variations by analyzing the interplay of host and tumor genotype and drug efficacy and toxicity. Having a reliable panel of prognostic and predictive markers will be critical in selecting an individualized and tailored chemotherapy regimen based on the particular tumor and host genotype. Although conflicting results have been reported, higher thymidylate synthase (TS) protein and mRNA expression levels in tumors have generally been associated with poor clinical outcome in patients treated with 5-FU–based chemotherapy regimens. However, the cause of the variability in TS expression still remains not fully understood, although several germ-line polymorphisms seem to affect the expression of TS, some of which have been found to have an effect on prognosis and the probability of response to 5-FU–based chemotherapy. This review will provide an update on pharmacogenomic studies of TS that were aimed at elucidating their role as prognostic and predictive markers. [Mol Cancer Ther 2009;8(5):1000–7] |
| Databáze: | OpenAIRE |
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