Skin cancer cells, like all cancer cells, are essentially super-charged cells. Mutations in their DNA allow the cells to replicate faster and turn off their natural self-destruct mechanism that keeps healthy cells in check. Since cancer cells multiply so quickly, they also need more resources than other cells.
“If you think of a really ramped-up racecar, that’s essentially the cancer cell, and then you’re thinking of a Volkswagen, that’s a normal cell,” said Gavin Robertson, the co-author of the study and professor of pharmacology at Pennsylvania State University in University Park.
Cholesterol is important to cell function, and in melanoma and other cancers, the pathways used to transport the cholesterol are so “ramped up” that the cells are essentially addicted to cholesterol, according to Robertson.
Melanoma treatments target specific molecular pathways that tumor cells use to transport cholesterol, but often the cell finds ways around the roadblock.
The study, published in Molecular Cancer Therapeutics, tested a compound known as leelamine in cultured melanoma cells.
Leelamine — which seems to act as an antimicrobial agent in pine trees — is unique because it is able to block three pathways of cholesterol transport. The researchers tested it along with several other compounds from a chemical library.
“This could be the first of a novel class of compounds,” Robertson said. “There isn’t a drug out there in the cancer arena that does this type of thing.”
But before it can be used on the market, it has to go through the usual long slog of clinical testing. One potential issue is that the drug could be a little too good at blocking cholesterol transport, and become toxic to healthy cells.
“What’s clear is that this drug is toxic to cells – most cells signal through these pathways,” said Ryan Sullivan, an oncologist at Massachusetts General Hospital in Boston.
But Sullivan was still interested in the compound.
“If they can somehow make this more tumor-specific, then I think they’ve got something,” he said.
One way to make sure the drug only affects the tumor cell would be to use a tumor-specific transporter such as a nanoparticle or a nanotube. A nanoparticle or nanotube could be loaded with the drug as well as a “homing” protein to find the tumor cell and deliver the drug directly to the cell.
But both leelamine and nanoparticles are a long way from being approved for use by the Food and Drug Administration. One of the hurdles in getting drugs off the ground isn’t just making sure they’re safe and effective, but also getting pharmaceutical companies interested in developing the drug. Clinical trials are very costly and are usually beyond the means of university-based research labs, so drugs need the financial resources of a drug company to get off the ground.
Melanovus Oncology, a drug-development company, will continue to test leelamine as a potential drug for melanoma. Robertson is the chief scientific officer of the company. But he said it will be another three to five years before the drug can be safely tested in human patients.
The best defense against melanoma, however, is prevention. Though light-skinned people are more at risk for developing all forms of skin cancer, anyone can develop it. The Centers for Disease Control and Prevention stresses the importance of wearing sunscreen and protective clothing when going outside, regardless of whether or not you burn easily. The CDC also recommends avoiding unnecessary exposure to ultraviolet light and monitoring for new, changing, or unusual skin moles.
Source: livescience.com by Cynthia McKelvey