The skin on your face is a roiling, competitive mix of mutant cells, even if you don’t have skin cancer. A group of scientists from Belgium and the UK examined “healthy” skin taken from four middle-aged people who were getting cosmetic surgery to tighten their eyelids. Though none of the subjects had ever had skin cancer, more than a quarter of their eyelid cells contained mutations associated with squamous cell carcinoma – which, unlike melanoma, is not deadly but can be inconvenient, painful and disfiguring.
The findings, published in this week’s issue of the journal Science, could shed light on how skin cancers develop and perhaps aid in the search for drugs that could prevent them or treat severe cases where surgery would be difficult. The researchers say nobody keeps exact statistics on these kinds of cancers but according to The American Cancer Society, there are approximately 700,000 cases of squamous cell skin cancer diagnosed each year in the U.S. and about 2.8 million cases of another common form, called basal cell cancer.
What was interesting was that the mutated cells weren’t just sitting there. Many were growing in clusters which the researchers refer to as clones. Some of these clones are probably cleaned up by the body’s immune system, but others might become malignant cells later on.
“We expected to see some mutations in normal skin, but we were surprised to see the burden of mutations per cell and the number of cells with mutations associated with cancer,” said one of the paper’s lead authors, Peter Campbell of the Wellcome Trust Sanger Institute in Cambridge, UK.
What we know, he said, is that it takes more than one mutation to start the formation of skin cancer, but scientists still aren’t sure how many mutations and which ones must accumulate to make a cell. Mutations happen when your DNA makes an error in copying itself as a cell divides. In skin, the mutation rate is accelerated by UV light from the sun (or tanning booths).
Campbell takes a Darwinian view – as do many more sophisticated cancer researchers. Some of the mutations that crop up in cells instruct them to grow extra fast, allowing groups of these cells, called clones, to outcompete their slower growing neighbor, like particularly prolific weeds taking over a yard.
The new findings help explain why skin cancers are so common considering that it takes a combination of at least three or four unlucky mutations to transform a healthy cell into a cancer cell. Some of the cancer-associated mutations prompt cells to grow faster than those around them. These growing clusters, or clones, still function like normal skin cells, but genetically they have already gone part way down the road to cancer. And with more of them, your odds go up that one of them will pick up other cancer-associated mutations as well.
Another surprise was that while basal cell cancers are more common than squamous cell, the researchers saw none of the mutations typical of this kind of cancer.
The small study raises a number of interesting questions, said Campbell: How many of these mutated clones will die out or be killed by the immune system? How much does our risk go up from sun exposure decades ago?
Yale cancer researcher Douglas Brash, who wrote an accompanying commentary piece on the findings, said that he led a similar but more limited experiment 20 years ago, and found that normal skin carried a high prevalence of mutations in a gene called p53, which is considered a tumor-suppressor gene. p53 mutations show up in many different kinds of cancer.
It would be nice, said Brash, if scientists could develop a targeted drug that could kill off the mutated and potentially cancerous cells. After all, many people today have sun-damaged skin and are prone to get cancer no matter how careful they are about avoiding sun in the future. Such a personalized approach has led to a few drugs for other kinds of cancer.
One drug is already on the market for basal cell cancer – vismodegib (trade name: Erivedge), by Genentech. It’s currently approved for cancers that can’t be treated with surgery. Studies have also shown that it helps people with disorder called Gorlin syndrome, which causes them to suffer dozens or even hundreds of basal cell cancers.
This new study suggests a complication for developing a similar drug for squamous cell cancer, since any drug that targeted the major cancer-associated mutations might also kill about 25% of a person’s skin. “If those were a systematic target you’d end up killing a lot of skin cells” Brash said.
But skin is apparently pretty good at regenerating itself, he said, and when he’s gone to dermatology conventions discussed the possibility of using skin cancer drugs that would kill 25 percent of healthy cells, dermatologists thought that wasn’t beyond what people could recover from.