Shirley Smith has faced so many tumors since she was diagnosed with estrogen-positive breast cancer in 1990, it is hard for her to keep track of the diagnoses and drugs prescribed for them.
She was on Tamoxifen for 5 ½ years to prevent a recurrence, but it failed, and she is not even sure what drug she is getting now at the Medical College of Georgia Cancer Center. The names don’t really matter to her as much as the constant in her life: faith.
“You’ve got God, you’ve got the doctors, and you can go on,” said Smith, 59, of Augusta.
Doctors have thrown a lot of compounds at breast cancer tumors to try to kill them, sometimes with serious side effects, but researchers at Georgia Health Sciences University might have come up with a cleaner way to get rid of the tumor: starve it to death.
In a study published recently in the Journal of Biological Chemistry, the GHSU team focused on a selective transporter of key amino acids into the tumor cells that help fuel rapid growth. The transporter protein, SLC6A14, is found in low levels in normal cells, said Dr. Vadivel Ganapathy, the chairman of Biochemistry and Molecular Biology at GHSU and the corresponding author on the study. Tumor cells need a large amount of essential amino acids in addition to large amounts of the amino acids glutamine and arginine.
The selective transporter for those amino acids was found at high levels in estrogen-receptor positive breast cancer cells but not in those tumors that lacked the receptor or in normal mammary tissues. A drug called alpha-methyl-dl-tryptophan blocked the transporter in estrogen-receptor positive breast cancer cells, which caused them to die off, but it did not affect the estrogen-negative tumors or normal tissue.
“That says two things,” Ganapathy said. “No. 1, the transporter could be a viable drug target. No. 2, if you can find a drug that blocks this transport system it is not likely to have any nonspecific side effects.”
There are already drugs to target hormone-based tumors, such as Tamoxifen, said Dr. Thomas Samuel, the director of the clinical breast cancer program at the cancer center.
“They last for some period of time but eventually the cells become resistant to those treatments,” he said. “So the hope is this particular pathway will be a new way to target these cells.”
Smith is a perfect example. She is getting a chemotherapy drug, Abraxane, but it is damaging nerves and causing tingling in her fingers. Samuel said that he would like to give her something besides chemotherapy but that researchers “don’t have any available at the moment. This is where the study would really be helpful.”
About 75 to 80 percent of breast cancers are estrogen-or progesterone-positive, or both, according to the College of American Pathologists.
Most chemotherapy works by killing rapidly growing cells, tumor cells and normal fast-growing cells such as hair, skin and blood, leading to side effects including hair loss, nausea and anemia. The tryptophan-derivative has the benefit that it is already being used in humans as a way to map serotonin-producing neurons during positron emission tomography scans, Ganapathy said.
“Therefore, all of the pre-clinical toxicology studies have been done to a large extent,” he said.
The compound “is very well-tolerated,” Samuel said.
“It’s a nutritional supplement,” he said. “You can buy it online; you can buy it in health food stores.”
In fact, because the compound can create a form of serotonin in the brain, it has actually been patented as an anti-depressant and, in one study, mice given the compound interacted better, Ganapathy said.
“It might be beneficial in order to modulate your mood,” he said. “It’s like taking Prozac.”
Ganapathy is pursuing grants to try to begin an early-phase clinical trial in people. Targeting the transporters could have implications for starving other, more difficult-to-treat-cancers, Samuel said.
“The hope is that this may be the beginning of a line of research that may lead to greater things down the road,” he said. “This sort of mechanism of targeting cells, not just breast cancer but any kind of cancer cell line, by their amino acid transport system is brand-new; it’s a whole new field.”