Demethylating Drugs to the Rescue: Epigenetic Therapy
In another recent study, researchers focused on inhibitors of enzymes necessary for maintenance of DNA methylation to drastically restrict tumor growth.
Since excessive DNA methylation occurring at promoters of genes caused the shutdown of genes necessary for cellular differentiation, researchers used two similar DNA demethylating agents (5-azacytidine and decitabine). Once DNA hypermethylation ceases to act as a repressor for the genes required for differentiation, cellular differentiation is restored and proliferation of tumor cells was curtailed. These demethylating drugs were able to drastically reduce tumor growth over sustained periods of time.
The sustained effects of these drugs are an important factor to consider. These drugs were able to sustain tumor reduction for 21 weeks or longer after treatment was withdrawn. DNA demethylating agents has shown striking promise and could help patients suffering from low-grade gliomas, as well as from recurrent tumors.
Earlier studies have shown that treatment with the inhibitor AGI-5198 did not affect DNA methylation. To test out the converse, a sensitization approach was utilized where DNA demethylating agents were employed first, followed by the mutant enzyme IDH1 inhibitor (AGI-5198). But no additive effect was observed when the therapies were combined.
Personalized Care and Genetic Cancer Treatments
With the burgeoning of personalized care, doctors will someday have access to the complete map of dysregulated genes in every patient. Harnessing that genetic map to attack cancer cells from different angles could transform cancer into a manageable illness.
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Turcan, Fabius AWM, Borodovsky A , et all. Efficient Induction of differentiation and growth inhibition in IDH1 mutant glioma cells by the DNMT inhibitor Decitabine. (2013). Oncotarget. Accessed October 9, 2013.
Borodovsky A, Salmasi V, et all. 5-azacytidine reduces methylation, promotes differentiation and induces tumor regression in a patient-derived IDH1 mutant glioma xenograft. (2013). Oncotarget. Accessed October 9, 2013.
Rohle D, Muller JP, Palaskas N, et all. An inhibitor of mutant IDH1 Delays Growth and Promotes Differentiation of Glioma Cells. (2013). Science. Accessed October 9, 2013.
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