Fine-tuning cancer therapies

Researchers have discovered epigenetic changes that contribute to one-fifth of cases of acute myeloid leukemia (AML), an aggressive cancer that arises out of the blood-forming cells in bone marrow. The mutations also play a role in a majority of low-grade gliomas, which are among the most-treatable brain tumors.

“The best way to treat a cancer is to understand it,” said Ricardo C.T. Aguiar, M.D., Ph.D., professor of medicine. “We have added to the understanding of a broad swath of cancers.”

The cancers carry a mutation called isocitrate dehydrogenase, or IDH. In the future, cancers will be classified by genetic mutations such as these rather than by location, said Dr. Aguiar, a hematology-oncology researcher at UT Health San Antonio Cancer Center, and senior author of the study.

IDH mutations alter an epigenetic process called RNA methylation, which leads to deregulation of hundreds of other genes and processes inside the tumor cell, the researchers found.

Epigenetic modifications change gene activity but don’t structurally change the body’s genetic blueprints. Diet, aging, environmental exposure and other factors can prompt epigenetic changes that amplify or silence certain genes.

A drug that inhibits these mutant enzymes is undergoing clinical trials. The discovery provides evidence for why the drug may help patients with acute myeloid leukemia and low-grade gliomas.

“Acute myeloid leukemia remains a very difficult-to-treat tumor and, unfortunately, the majority of patients still die of their disease,” Dr. Aguiar said. “By better understanding how the IDH-dependent cancers work, we may be able to fine-tune future therapies and improve survival.”