Scientists at the Institute of Cancer Research have discovered that the BRAF gene mutation is often the first event in a cascade of genetic changes - this causes cells to become cancerous after excessive exposure to the sun, leading to melanoma, the most deadly form of skin cancer.
Scientists were already aware that the BRAF gene was frequently damaged in patients with melanoma but until now it was unclear if this was a cause or effect of the cancer and the new revelation could lead to better treatments for the deadly disease.
Lead researcher Professor Richard Marais says the study shows that the genetic damage of BRAF is the first step in skin cancer development and understanding this process will help them develop more effective treatments for the disease.
Scientists are optimistic that once the genetics behind skin cancer are clear it will lead to the development of targeted drugs that can fix the faulty genetic machinery.
Although the study was carried out in mice, the researchers said that melanomas which develop in the animals closely resemble those that develop in humans.
Though melanoma accounts for only a small percentage of skin cancers, it is the root cause of most skin cancer deaths.
Melanomas occur when pigment-producing skin cells called melanocytes proliferate in an uncontrolled manner and over-exposure to sunlight is the cause of at least two-thirds of cases when DNA in sun burnt skin cells becomes damaged, leading to the genetic mutations.
Melanoma is the most deadly and serious form of skin cancer and sun exposure is the main -and most preventable risk factor - other melanomas develop as a rule from normal moles.
Warning signs to look for include - two halves of a mole do not look the same - edges of a mole which are irregular, blurred or jagged, a mole with uneven colour, with more than one shade and a mole wider than 6mm.
The risk of developing melanoma can be reduced by staying out of the sun between 1100 and 1500, never getting burnt, wearing a t-shirt, hat and sunglasses and using factor 15+ sunscreen - extra care must be exercised with children and sun exposure.
The research is published in the journal Cancer Cell.
Several synthetic HDAC inhibitors are under study for a variety of cancers at institutions such as the MCG Cancer Center. Unfortunately, just like the newly found GPR109A receptor, cancer also silences the SLC5A8 butyrate transporter. In his current study, the researcher found the receptor was silenced in 15 of 18 colon cancer patients.
"Colon cancer does not want butyrate produced by bacteria to come inside so it silences the transporter. It also does no want butyrate to act on the cell from the outside so it silences the receptor," Dr. Ganapathy says. "It does not want to have anything to do with butyrate."
Because the compounds that reactivate the receptor also reactivate the transporter, finding a way to mitigate cancer's attempts to silence the genes would create a two-prong attack against the cancer.
Mega doses of butyrate reportedly taste bad. But Dr. Ganapathy believes taking large amounts of niacin, something many patients already do for high cholesterol, is a good substitute. In fact, he wants to move ahead with clinical trials that compare the course of colon cancer patients who eat a high fiber diet or receive butyrate or niacin therapy along with taking DNA methylation inhibitors that keep GPR109A open for business.
He also wants to determine if his theory that inflammation also suppresses the receptor holds true. "We think receptor activation by butyrate suppresses inflammation, thereby suppressing progression of inflamed cells into cancer cells." If he's correct, targeting the receptor also may provide a new treatment for inflammatory bowel disease.
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