Genomics & Proteomics：揭开癌症遗传学之谜
With drugs like decitabine, he says, there is the possibility of having pleiotropic effects on tumor cells. That is, targeting more than one protein or pathway. In particular, the expression of tumor-suppressor genes—which is turned off through DNA methylation—has been targeted by hypomethylating agents like decitabine. “So if we can turn those genes back on by inhibiting DNA methylation in cancer cells, we think that we could have a positive effect on reversing the tumorigenic phenotypes.”
So far, the FDA has only indicated decitabine for myelodysplastic syndrome—a precursor to myelogenous leukemia. However, Bearrs says the application of decitabine should not be limited to liquid tumors, and that drugs similar to decitabine are already being investigated for solid tumors. He predicts that these investigational hypomethylating agents will likely be used in combination with a class of compounds known as histone deacetylase inhibitors, which block the epigenetic event, histone deacetylation—another regulatory mechanism that can activate the expression of specific genes.
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