Scientists Reprogram Cancer Cells With Low Doses of Epigenetic Drugs (azacitidine, decitabine, epigenetic drugs)

Scientists Reprogram Cancer Cells With Low Doses of Epigenetic Drugs:

• Drugs previously considered too toxic for human use.
• Cancer stem cells were a target of these agents.
• Study by Stand Up To Cancer Dream Team published in Cancer Cell.

( Clinical trials in breast and lung cancer have begun in patients with advanced disease, and trials in colon cancer are planned. )

CHICAGO — Experimenting with cells in culture, researchers at the Johns Hopkins Kimmel Cancer Center have breathed possible new life into two drugs once considered too toxic for human cancer treatment. The drugs, azacitidine and decitabine, are epigenetic drugs and work to correct cancer-causing alterations that modify DNA.
The researchers also found that the drugs took aim at a small but dangerous subpopulation of self-renewing cells, sometimes referred to as cancer stem cells, which evade most cancer drugs and cause disease recurrence and spread.
In a report published in the March 16, 2012, issue of Cancer Cell, the Johns Hopkins team said their study provides evidence that low doses of the drugs cause antitumor responses in breast, lung and colon cancer cells. They will discuss their work at a Stand Up To Cancer press event on April 1, 2012, at 1:00 p.m. CT in Room 10 A/B/C of the Hyatt Conference Center, adjacent to the McCormick Place Conference Center.
Conventional chemotherapy agents indiscriminately poison and kill rapidly dividing cells, including cancer cells, by damaging cellular machinery and DNA.
“In contrast, low doses of azacitidine (AZA) and decitabine (DAC) may reactivate genes that stop cancer growth without causing immediate cell killing or DNA damage,” said Stephen Baylin, M.D., Ludwig professor of oncology and deputy director of the Johns Hopkins Kimmel Cancer Center in Baltimore, Md.

Phase 1b-2a study to reverse platinum resistance through use of a hypomethylating agent, azacitidine, in patients with platinum-resistant or platinum-refractory epithelial ovarian cancer

BACKGROUND: Sequential treatment with azacitidine can induce re-expression of epigenetically silenced genes through genomic DNA hypomethylation and reverse carboplatin resistance of epithelial ovarian cancer cells. A phase 1b-2a clinical trial of this sequential combination of azacitidine and carboplatin was initiated in patients with platinum-resistant or platinum-refractory epithelial ovarian cancer.