New study shows epigenetic drugs can reprogram cancer cells

Mar 28, 2012 20:01 GMT  ·  By

Johns Hopkins Kimmel Cancer Center (JHKCC) investigators say that small amounts of two epigenetic drugs could be used to reprogram cancer cells, helping to cure tumors. These chemicals were thought to be way too toxic for use on humans at first, but the team developed a way to make them safe.

Both azacitidine and decitabine are epigenetic drugs, which means that they can influence the DNA abnormalities that facilitate the development of cancer. However, introducing them into the body has been demonstrated to have adverse side-effects.

One of the most important aspects the team discovered in this investigation was that the two drugs – when used in low doses – appeared to prefer attacking the elusive cancer cell populations that cause the recurrence and spread of cancer.

These are called cancer stem cells (CSC), and are somehow able to elude the action of all other cancer drugs. By destroying this cellular population, the two chemicals basically deprive the disease of its main source of cellular replenishment, leaving the other cells more susceptible to conventional therapies.

During a new series of experiments, scientists observed anti-tumor responses in breast, lung and colon cancer cells. Details of the work were published in the March 16 issue of the journal Cancer Cell, the American Association for Cancer Research (AACR) reports.

If implemented, the new approach to treating cancer would be a lot safer and more elegant than standard chemotherapy, where drug cocktails attack all rapidly-dividing cells (including healthy ones), and destroy their DNA and cellular machinery.

“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,” Stephen Baylin, MD, says.

The investigator holds an appointment as the Ludwig professor of oncology and deputy director of the Johns Hopkins Kimmel Cancer Center in Baltimore, Maryland. AZA and DAC were abandoned by most scientists after it was found that they are very toxic to healthy cells at standard concentrations.

However, the drugs already have the approval of the US Food and Drug Administration (FDA), for use in treating MDS and chronic myelomonocytic leukemia, a form of blood cancer.