Early research suggests that vitamin D, a compound the human body makes naturally when exposed to the sun and essential to healthy bones, has the potential to be used as a starting point in the creation of new drugs to treat skin cancer.
Scientists in recent years have shown that vitamin D3, one form of vitamin D, appears to have the ability to stop a broken network of proteins linked to the development of the most common type of skin cancer – basal cell carcinoma. Basal cell is also the most prevalent of all cancer types in the United States, with more than 2 million diagnoses each year.
The protein network, called the Hedgehog signaling pathway, is vital during embryonic development, but usually remains shut off in adults. Sometimes though, the Hedgehog pathway gets reactivated. When this happens it can cause out-of-control cell growth that leads to some types of basal cell cancers.
The discovery of the linkage between vitamin D3 and the Hedgehog pathway is what spurred University of Connecticut chemist and researcher Kyle Hadden, Ph.D., to start trying to create chemical compounds based on vitamin D that could help treat basal cell cancer. With the help of a 4-year, $716,000 grant from the American Cancer Society, Hadden, is trying to engineer a version of vitamin D3 that possesses only its anti-cancer abilities, but leaves out the potentially harmful effects it could have at the high does necessary to treat cancer.
Vitamin D essentially increases the amount of calcium in the body; and too much calcium can cause problems like nausea and vomiting and can impact a person’s mental state and heart rhythms. “You can’t give a patient vitamin D3 itself over an extended period of time because it would have detrimental side effects,” says Hadden. “We want to create a drug to do one thing specifically – we want it to selectively target the Hedgehog pathway.”
Hadden notes that there is currently one Hedgehog inhibitor drug on the market, but it stops working over time. “We are hopeful that our compound would continue to work over time … we want to be better than the current therapy.”
Every 4 to 5 months, Hadden’s lab creates about 20 new vitamin D3 analogs – chemical compounds similar to the vitamin, but with certain components changed. Then, they spend about 1 month testing the batch on mouse cells grown in the lab. Over the past 3 years, Hadden has made several hundred different vitamin D3 compounds. “We have learned a lot and we have moved closer [to a viable compound].”
Clinical Trials and Beyond
The next step is to work with a collaborator to test the compounds in live mice, which he hopes to start doing in the next 6 months. Hadden says that if in the next few months his lab creates a compound that “really blew us out of the water,” a drug might potentially make it to clinical trials (studies in people) in 3 to 5 years.
Those with basal cell carcinoma aren’t the only ones who stand to benefit. Hadden notes that a type of brain cancer seen primarily in children – called medulloblastoma – is also linked to the Hedgehog pathway. “Right now there are treatments that can extend life, but there is not a good drug or treatment that gets anywhere close to a cure,” says Hadden. He is looking at how the vitamin D3 analogs he is creating could also be used to treat this type of cancer.
In addition to working on the vitamin D3 compounds, Hadden is also trying to determine whether the ways the body moderates vitamin D3 is part of the reason the Hedgehog pathway malfunctions in the first place to cause cancer.