Melanoma develops in melanocytes—the cells that produce melanin, the pigment that gives us our skin color. Any part of the skin that has contact with the sun has cancer risk potential, but melanoma may also form in the eyes and rarely in the intestines and other internal organs. The precise cause of melanoma isn’t entirely understood, but it is known that limiting UV radiation exposure can help reduce the risk. Oftentimes, the first signs of skin cancer will be the development of an irregularly shaped mole on the body, but sometimes it can occur on otherwise normal-appearing skin. It is thought that DNA damage in skin cells is what leads to mole formation, but it isn’t entirely clear, as a combination of environmental and genetic factors may play a role in cancer development. The following are risk factors for melanoma cancer development:
- Fair skin: These individuals have less pigment or melanin, which is known to protect against the harmful rays of the sun. Those with darker complexions do have increased protection, but melanoma can still develop in these groups too.
- History of sunburn: Having one or more severe blistering sunburns can increase the risk.
- Excessive UV light exposure: Harmful rays from the sun or tanning beds.
- Living closer to the equator: The sun’s rays are more direct near the equator. This means higher amounts of UV light reach these areas.
- Having many moles or unusual moles: Having more than 50 ordinary moles on the body indicates an increased risk of melanoma. Irregular looking moles, also called dysplastic, indicates increased risk.
- Family history: If any relative like a parent or sibling has had melanoma, you have an increased risk.
- Weakened immune system: These individuals also have an increased risk for skin cancer development.
The new research in question used mouse models to help study this complex disease, but the researchers stress that mouse melanoma is far less complex than its human counterpart. They used this to their advantage to better study key histopathological features of the human disease by identifying a dozen new genes in rats that are likely to play a key role in the development and progression of human melanoma. They identified one gene called FES, establishing it as an important contributor to both mouse and human melanoma.
The FES gene was previously found to be able to transform normal cells into cancer cells under certain conditions, but its role in melanoma was found to be very different.
“To our surprise, we obtained clear evidence that FES strongly suppresses melanoma growth and viability. Its expression is silenced in more than 30% of human melanoma lesions. Importantly, we showed that FES deletion in mice accelerated the growth of melanoma tumors,” said, Prof. Jean-Christophe Marine.
The researchers go on to say that this gene modulated the WNT signal pathway—a key cancer pathway that is activated in virtually all cases of melanoma. Despite this pathways recognition, researchers are still unsure of its mechanisms for cancer activation, with the FES gene now known as one route for activation in about 30 percent of cases. This identification opens the doors to the possibility of new treatments that activate the FES gene helping treat melanoma.
“We will definitely further explore this new putative therapeutic strategy. Importantly, in the same time, our data raise concerns about ongoing clinical trials with broad-spectrum tyrosine kinase inhibitors. Some of these inhibitors inactivate FES and therefore may lead to undesired effects.”