Rapid and progressive melanoma development is most often attributed to genetic mutations. However, a recent study by University of Zurich researchers has found that epigenetic factors play a key role in melanoma’s metastatic potential, paving new avenues into potential cancer therapies.
Many of the melanoma drugs available today specifically target signaling pathways that are activated due to mutations in certain genes. In fact, some of these drugs have proved extremely beneficial in some clinical studies, significantly extending patient’s lives. Nonetheless, in many occasions, patients start to become resistant to these drugs, which ultimately results in melanoma progression and tumor spread throughout the body.
Epigenetic factors are responsible for controlling how a particular gene is “read”, which although not directly interfering with the gene sequence, has the power to change the way some genes and chromosomal segments are packed in different densities.
In their study titled “The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors”, published in Nature Communications, the research team led by Professor Lukas Sommer, from the University of Zurich’s Institute of Anatomy, has discovered the mechanisms behind this active behavior of melanoma cells. According to the authors, upon different conditions, cancer cells can identify different genes and use them in their favor.
The team used a melanoma mouse model, and found that genetic ablations of the epigenetic modifier EZH2, could stabilize tumor progression and avoid metastases formation. Furthermore, in human melanoma cells, inactivation of EZH2 could successfully stop proliferation and diminish the invasive potential of these cells.
Additionally, the team used a synthetic inhibitor and suppressed the activity of EZH2, observing that this approach was also capable of preventing the growth and malignant spread of cancer cells in both in vitro and in vivo models of melanoma.
“To our astonishment, we were able to use the approach to influence the progression of the disease, even if tumors had already developed,” explaind Professor Sommer in a news release.
The results from this study open up the possibility of targeting epigenetic factors like EZH2 for future cancer treatments, in particular upon combination with currently available drugs.