By Manel Esteller
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Similarly, in protocol 8921 with SQ 5-azacytidine, the CR, PR, and HI rates were 17%, 0%, and 23%, respectively. After the encouraging results seen in the phase II studies, the CALGB initiated a randomized phase III trial: 191 patients were randomized to 5-azacytidine (75 mg/m2 SQ daily × 7 days every 28 days) vs. 30 The median time to acute myeloid leukemia (AML) transformation or death for patients receiving supportive care vs. 5-azacytidine was 12 vs. 007). When the data was reanalyzed using the IWG criteria, the overall response rate was 47% (CR 10%, PR 1%, and HI 36%) vs.
However, the lack of any gene mutation or CpG island promoter methylation may cause some concern to classical researchers: the epigenetic inactivation of p21WAF1 by promoter hypoacetylation-mediated silencing offers an attractive alternative. Other genes altered in this manner in cancer cells continue to be identified, but more work is needed in this area. HDAC inhibitors may achieve some of their antitumoral effects through reactivation of these new types of dormant tumor-suppressor gene. 5 Histone-Modifying Enzymes and Cancer The analysis of expression patterns of histone-modifying enzymes enables the discrimination of tumor samples from their normal counterparts and the clustering of the tumor samples according to cell type [30], which implies that these proteins have tumor-specific roles in cancer development.
World J. Gastroenterol. 2004;10:2643–2646. 28. Jenuwein T, Allis CD. Translating the histone code. Science. 2001;293:1074–1080. 29. Herranz M, Esteller M. DNA methylation and histone modifications in patients with cancer: potential prognostic and therapeutic targets. Methods Mol. Biol. 2007;361:25–62. 30. Ozdag H, Teschendorff AE, Ahmed AA, Hyland SJ, Blenkiron C, et al. Differential expression of selected histone modifier genes in human solid cancers. BMC Genomics. 2006;7:90. 31. Guarente L. Sir2 links chromatin silencing, metabolism, and aging.
