Are Epigenetics the New Osteosarcoma Solution?

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Researchers from Case Western Reserve University accomplished a groundbreaking medical triumph. In partnership with six other institutions, the team inhibited cancer cells from spreading to different parts of the body. Focusing on osteosarcoma and with an emphasis on epigenetics, the research is truly one of the first of its kind. Keep reading to learn more, or follow the original source here.

In the course of their study, researchers prevented the spread of osteosarcoma in mice. The use of epigenetic techniques allows scientists to keep cancerous cells localized and prevent them from spreading to the lungs. The team included members of the National Cancer Institute and Cleveland clinic. The journal Nature Medicine since published their study.

A large number of deaths from osteosarcoma occur as a result of cancer reaching the lungs. Many cases of osteosarcoma strike those between the ages of 10 and 30. Clinical outcomes remained stagnant for nearly 30 years. Furthermore, there exists no reliable therapies to combat metastasis, or the movement of cancer cells.

According to the study’s senior author, over 90% of cancer deaths result from metastasis. Scientists know many genes related to metastasis, but the method by which they work remains nebulous.

This new study’s findings, however, “demonstrate that altered gene-enhancer activity is fundamental to a cancer cell’s ability to metastasize.”

Gene enhancers are short bits of DNA. In coordination with specific proteins, these enhancers effectively work as on/off switches. The pattern and nature of these switches helps define a cell’s character. Failed regulation of the same switches, however, seems to lead to disastrous consequences. Tumor formation and the spread of cancer cells appear to all be tied to these switches.

Using a series of epigenetic profiling tests, the research team identified a specific cluster of enhancers.

The group, labeled metastatic variant enhancer loci (Met-VELs) exists near lung metastases in osteosarcoma patients. After identifying these enhancers and confirming they were involved in the metastatic process, researchers moved on to preventing them. Researchers showed that the use of BET inhibitors helps prevent the growth of osteosarcoma cells in the lungs. This results from the way in which BET inhibitors disrupt Met-VELs.

Researchers also demonstrated that metastatic activity can be depressed by blocking expression of Met-VEL regulated genes. The deletion of a single Met-VEL responsible for regulating F3 expression also appeared to be similarly useful.

The new study represents not only a novel approach, but a sprint away from tradition. The currently accepted model for metastasis largely focuses on gene mutations. Epigenetics is, by contrast, unexplored. Yet the experiments led by the Case Western team show great promise in mice by removing specific cells crucial to the caner’s growth rather than focusing all efforts on primary tumors.


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