The ideal substance to prevent cancer would block tumor growth without causing unpleasant or dangerous side effects.
Researchers at the School of Medicine are reporting that a compound related to vitamin A shows promise in preventing or slowing tumor growth in mice prone to lung cancer. The compound, called bexarotene, doesn’t cause the severe skin irritations that have limited the use of other vitamin A derivatives in cancer therapies.
“In the cancer-prevention field, you look for drugs that can be given to healthy patients who have a higher risk of developing cancer,” said Ming You, M.D., Ph.D., director of the Chemoprevention Program at the Siteman Cancer Center. “These patients wouldn’t want to take a medication that makes them feel sick when they don’t have cancer.”
In other studies, bexarotene showed some promise in cancer treatment. It extended survival in patients with non-small cell lung cancer, the most common type of lung cancer and one that has a five-year survival rate of less than 5 percent when diagnosed at the advanced stage.
In the current study, which will appear in an upcoming issue of Oncogene, Yian Wang, M.D., Ph.D., associate professor of surgery; You, professor of surgery; and their colleagues demonstrate that lung cancer-susceptible mice receiving non-toxic doses of bexarotene ended up with fewer and smaller benign and malignant tumors than mice that were not treated with bexarotene.
The researchers saw an almost 50 percent reduction in terms of total tumor burden in mice who were given bexarotene for 12 weeks after the animals had already developed benign tumors following injection of a lung carcinogen.
Bexarotene also inhibited the progression of benign to malignant tumors by about 50 percent.
The mice were engineered to have the genetic alterations seen in human lung cancers, so they readily developed lung cancer when given known lung carcinogens.
“Seeing this magnitude of response in such a strongly susceptible mouse suggests bexarotene is a potentially viable lung cancer-prevention candidate,” You said.
Researchers have studied vitamin A analogs called retinoids for several years as potential chemotherapeutic agents because they help regulate cell division, growth, differentiation and proliferation. A new class of these vitamin A relatives has been created that includes bexarotene. These substances are called the rexinoids, which tend to be much less toxic than retinoids.
Among them, bexarotene has so far shown the most promise as a chemopreventive medicine. However, although it causes far fewer side effects, bexarotene does have the effect of increasing blood lipid levels in many patients, so patients often need to take a drug to lower their cholesterol and triglyceride levels.
A new rexinoid called UAB30, just becoming available for laboratory studies, seems to have the potential to reduce even the high-lipid side effect.
“We will be testing this new compound, too,” You said. “And if it turns out to be effective, these rexinoids will most likely become candidates for clinical trials in patients with precancerous nodules or bronchial dysplasia.
“If the trials show reduction of cancers, I think these drugs may well become routinely used for lung cancer prevention.”