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Using Epigenetics To Understand Metastasis May Lead to Novel Mesothelioma Treatment

UK Researchers Identify Gene That May Limit Metastasis

Researchers know that the best way to increase survival in cancer patients is to keep the disease from spreading to other areas. For aggressive cancers like pleural mesothelioma, cancer cells can outfox even the strongest treatments and metastasize, leaving patients with poor survival. Now, researchers report that through epigenetics they discovered a novel way to inhibit the spread of cancer that could lead to a new treatment that ends cancer growth.

In a break from traditional research looking into gene mutations, a team of researchers from Case Western Reserve University School of Medicine of Cleveland, Ohio, used epigenetics, the study of how genes are turned on and off, as a way to distinguish the differences in primary tumors and metastatic tumors. The team knew that “enhancer activity,” or the genes’ ability to turn switches on or off,  “lend cells their unique characteristics” and contribute to normal development.

However, faulty activity within the cells can lead to tumor development and the spread of cancer. Upon further inspection of the metastasized tumors, the researchers discovered the on-off switches were “in different positions than in the cells of the source tumor.”

“Metastasis results from a complex set of traits acquired by tumor cells, distinct from those necessary for tumors to form in the first place,” said the study’s lead author, James J. Morrow, PhD, a medical student in the Medical Scientist Training Program at Case Western Reserve University School of Medicine. “So based on the knowledge that enhancers drive both normal cell development and tumor-formation, we hypothesized that they may play a similar role in the transition of cancer cells from one developmentally distinct tissue to another during metastatic progression.”

Metastasis, according to researchers, is the cause of nearly 90 percent of cancer deaths. Researchers agree that understanding how to stop metastasis is critical for increasing survival in mesothelioma, an asbestos-caused cancer, and other cancers.

Using mouse models of bone cancer (osteosarcoma) cells, the team wanted to find a way to halt the spread of the cancer to the lungs. Through epigenomic profiling, the team found “bunched clusters of enhancers,” metastatic variant enhancer loci (Met-VELs), near the cancer cells that had metastasized to the lungs. Turning to BET inhibitors, a promising class of anti-cancer drugs now in clinical trials, to interrupt the Met-VELs, the researchers were able to inhibit the cancer growth in the lungs.

Based on the success, the researchesr concluded Met-VELs “may be suitable targets” for treatments targeting metastasis.

Using epigenetics as a new approach for finding an effective treatment could bring the breakthrough needed for halting cancer growth and for increasing survival in the nearly 3,000 Americans diagnosed with mesothelioma each year.

The study was published Jan. 15 online in Nature Medicine.

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