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Changes in DNA Methylation in Neoplasia: Pathophysiology and Therapeutic Implications
Abstract
Methylation of DNA is a biochemical modification that can influence gene expression and is involved in inactivating one of the two X chromosomes in women. Evidence that has accumulated in the past 10 years suggests that cancer cells usurp this physiologic mechanism and use it to their benefit by inactivating tumor suppressor genes and related proteins. However, the primary structure of the affected proteins remains intact; reversal of abnormalities in DNA methylation may therefore restore the tumor-suppressive function of these genes and provide a novel approach to cancer therapy. Two demethylating drugs, 5-azacytidine and 5-aza-deoxycytidine, are currently being tested in clinical trials, and several others are in preclinical development. In this article, the biological rationale for targeting aberrant methylation in cancer therapy is reviewed and completed phase I and II trials of this approach, some of which show promise for treatment of hematologic malignancies, are summarized.
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Cites
CpG-rich islands and the function of DNA methylation
Bird, A. P. (1986) · Nature · doi:10.1038/321209a0 · Cited by 3,777
Cellular differentiation, cytidine analogs and DNA methylation
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Cited by
Jaenisch, R., & Bird, A. (2003) · Nature Genetics · doi:10.1038/ng1089 · Cited by 6,325
A simple method for estimating global DNA methylation using bisulfite PCR of repetitive DNA elements
Yang, A. S. (2004) · Nucleic Acids Research · doi:10.1093/nar/gnh032 · Cited by 1,033
DNA hypomethylation and human diseases
Wilson, A. S., Power, B. E., & Molloy, P. L. (2007) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2006.08.007 · Cited by 804
Valinluck, V. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh739 · Cited by 756
Natsume, A., Wakabayashi, T., Tsujimura, K., Shimato, S., Ito, M., Kuzushima, K., Kondo, Y., Sekido, Y., Kawatsura, H., Narita, Y., et al. (2008) · International Journal of Cancer · doi:10.1002/ijc.23407 · Cited by 93
Sandoval, J. E., Huang, Y.-H., Muise, A., Goodell, M. A., & Reich, N. O. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.006795 · Cited by 66
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Gene silencing - a new theory of aging
Burzynski, S. R. (2003) · Medical Hypotheses · doi:10.1016/s0306-9877(03)00050-1 · Cited by 34
Snahnicanova, Z., Kasubova, I., Kalman, M., Grendar, M., Mikolajcik, P., Gabonova, E., Laca, L., Caprnda, M., Rodrigo, L., Ciccocioppo, R., et al. (2020) · Clinical and Experimental Medicine · doi:10.1007/s10238-019-00601-7 · Cited by 29
The Synergistic Effect of 5-Aza-2′-Deoxycytidine and 5-Fluorouracil on Drug-Resistant Tumors
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Metadata
- Authors
- Santini, V., Kantarjian, H. M., & Issa, J.-P.
- Venue
- Annals of Internal Medicine
- Publisher
- American College of Physicians
- Published
- 2001-04-03
- Volume
- 134
- Issue
- 7
- Pages
- 573-586
- ISSN
- 0003-4819 (ISSN-L)
- 1539-3704
- OpenAlex
- W2145337538
- Cited by
- 414
- References
- 2
- FWCI
- 11.72
- Type
- journal article
- Language
- en
- Open access
- closed
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