Therapeutic implications of the epigenome on anticancer
therapy
Inhibition of the main DNA methylation enzyme DNMT1 and the
demethylase/ MBD2 results in a marked anticancer effect and has potential
in anticancer therapy. We developed antisense and direct inhibitors of DNMT1
with demonstrated preclinical anticancer effect. A DNMT1 antisense molecule
is currently in clinical trials (directed by MethylGene Inc.). Inhibition
of MBD2/demethylase also showed anticancer activity in preclinical studies.
We are interested in identifying under members of the epigenome that might
serve as anticancer targets.
Discussion of our model on the anticancer potential of DNA
methylation and demethylation inhibitors will be found in: {Szyf M., 1994,
Trends Pharmacol Sci, 15(7), 233-8, Szyf M., 1996, Pharmacol Ther, 70(1),
1-37; Szyf M., 1998, Cancer Metastasis Rev, 17(2), 219-31, Szyf M. et al.,
2000, Ann N Y Acad Sci, 910, 156-74; discussion 175-7, Szyf Moshe, 2000, Current
Drug Targets, 1(1), 101-118, Szyf M., 2001, Trends Pharmacol Sci, 22(7), 350-354.,
Szyf M and Detich N, 2001, Prog Nucleic Acid Res Mol Biol, 69, 47-79}