Pharmacogenomics of thymidylate synthase in cancer treatment

Frontiers in Bioscience : a Journal and Virtual Library
Peter V Danenberg

Abstract

Cancer drugs such as 5-fluorouracil (5-FU) that target the enzyme thymidylate synthase (TS) have been and are still being widely used in cancer treatment, but as with other anti-cancer drugs, the majority of tumors do not respond to the treatment, whereas the patients still suffer drug-related toxicity. The most recent attempts at improving cancer treatment have taken the pharmacogenetic approach of identifying biochemical response determinants for response, so that patients with suboptimal determinants who unlikely to respond can be identified prior to treatment. Studies to date indicate that high intratumoral levels of TS gene expression or TS protein generally predict for non-response, whereas low levels are associated with a high response rate. Measuring these determinants requires tumor tissue and, in the case of gene expression, a technically demanding quantitative PCR procedure. Thus, considerable interest was generated by data suggesting that the variable number of a 28 base-pair (bp) segment in the promoter region of the TS gene was associated with TS gene expression and/or protein expression, as well as with tumor response to 5-FU therapy, toxicity and patient survival. However, not all studies have obtained the same ...Continue Reading

Citations

Jun 24, 2008·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Stanley R Hamilton
Jan 15, 2008·Pharmacogenetics and Genomics·Georg LurjeHeinz-Josef Lenz
Nov 28, 2007·Clinical Colorectal Cancer·Georg LurjeHeinz-Josef Lenz
Jul 29, 2008·International Journal of Cancer. Journal International Du Cancer·Marleen J GosensAdriaan J van den Brule
Jan 7, 2011·Journal of Oncology·Muhammad Wasif SaifKostas Syrigos
Feb 15, 2012·Expert Opinion on Therapeutic Patents·Pablo ÁlvarezAntonia Aranega
Nov 24, 2007·Pharmacogenomics·Marie-Christine Etienne-GrimaldiGérard Milano
Aug 24, 2013·Genetic Testing and Molecular Biomarkers·Violetta Sulzyc-BielickaMarek Drozdzik
Oct 7, 2005·Pharmacogenomics·Kim RobienCornelia M Ulrich
Apr 23, 2009·Molecular Cancer Therapeutics·Georg LurjeHeinz-Josef Lenz
Sep 27, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Rémy LargillierGérard Milano

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