Just when it seems that scientists are winning the fight against
cancer, tumors hit below the belt by developing resistance to
chemotherapies. But researchers at the University of Glasgow and
TopoTarget Prolifix Ltd. have shown that delivering a 1-2 punch
of epigenetic drugs could allow the chemotherapeutic agent
cisplatin to knock out resistant tumors. Cisplatin, a drug used
to treat some forms of cancer, triggers tumor cell apoptosis by
causing DNA crosslinking. Cancer cells can acquire cisplatin
resistance by several mechanisms, including epigenetic
inactivation of the MLH1 DNA mismatch repair gene. Previous
studies have shown that the treatment of cisplatin-resistant
cell lines with decitabine, a DNA methyltransferase inhibitor,
induces the partial reversal of DNA methylation, re-expression
of MLH1, and sensitivity to cisplatin. But the dose-limiting
toxicity of decitabine, as well as the eventual re-methylation
of genes in treated cells, has limited the clinical use of this
epigenetic drug. In the presen