A Surprising Find: Anti-Allergy Drug Reduces Tumor Growth
Conquest - Spring 2007
By Scott Merville
Craig Logsdon’s five-year search for an agent to treat pancreatic cancer may be nearing an end. A common anti-allergy drug might hold the essential properties needed to destroy this aggressive type of tumor.
In the Journal of the National Cancer Institute, Logsdon and his team report that combining the drug cromolyn with chemotherapy was nearly three times better at retarding growth of human pancreatic tumors in mice compared to the chemotherapy agent gemcitabine alone.
Craig Logsdon, Ph.D. (left), and Senior Research Scientist Thiru Arumugam, Ph.D., found that combining an anti-allergy drug with chemotherapy was significantly better at slowing the growth of human pancreatic tumors implanted in mice compared to using chemotherapy alone.
The finding may lead to a new treatment for patients with pancreatic cancer, which is believed to be the most lethal of all cancers. More than 95% of patients diagnosed with the disease die from it, and one-half of those deaths occur in the first six months after diagnosis.
“Our goal is to offer longer life to these patients, and the combination of these two agents may well do that,” says Logsdon, Ph.D., professor in the Department of Cancer Biology and the study’s lead author.
According to Logsdon, the cromolyn-gemcitabine combination reduced pancreatic cancer growth in mice by 85% compared to the control group. Cromolyn also had a good effect on its own, reducing tumor growth by 70% as opposed to 50% when gemcitabine was used alone.
“Cromolyn seems to reduce survival mechanisms in pancreatic cancer cells enough that when gemcitabine is added, the chemotherapy is more effective,” Logsdon says. “This is good because chemotherapy normally has very little effect in these patients.”
A twist of fate
The relationship between how cromolyn controls allergies and its anti-tumor effect in pancreatic cancer remains unclear. However, Logsdon discovered that cromolyn can bind to a specific protein produced by cancer cells and block that protein’s ability to interact with a receptor that stimulates cancer cell growth, survival and spread.
“Through serendipity and basic science sleuthing, we may now have something that helps patients,” Logsdon says.
Logsdon explains that he searched for genes that produced proteins secreted only by cancer cells, which would then loop around and act on the cancer cell through a receptor on the cell surface. “That way, we could have two potential targets — the secreted protein and the receptor.”
After slogging through dozens of potential genes, Logsdon fixed his attention on the protein S100P and found that it was highly specific to pancreatic cancer. It was not found in normal pancreatic cells.
Using gene-silencing techniques, Logsdon further discovered that when the protein S100P is disabled, cancer growth is slowed. “S100P plays a role in tumor development because it causes cancer cells to grow faster, survive better and become more invasive,” he notes.
Logsdon found that S100P interacts with a receptor known as RAGE, which also plays a role in diabetes, arthritis and Alzheimer’s disease. If RAGE is blocked in pancreatic cancer cells, addition of synthetic S100P to the tumor doesn’t accelerate growth.
While Logsdon was defining S100P in pancreatic cancer, a Japanese research team working on allergies ran an experiment to see which proteins “stuck” to cromolyn and other anti-allergy drugs. Several members of the S100 gene family, including S100P, did.
Based on these findings, Logsdon then applied cromolyn to pancreatic cancer cell lines and found that tumor growth slowed. A larger effect was seen when the chemotherapy agent gemcitabine was combined with cromolyn.
Logsdon suspects that cromolyn may have other anti-tumor effects, a theory which he is currently testing. “For me this is pretty thrilling,” he says. “In a relatively short time, we have gone all the way from discovering a molecule to preparations for a clinical trial.”Although cromolyn is off-patent and widely available, it has been used only as a topical agent (through an inhaler, nasal spray and eye drops), so the research team is studying how to deliver the drug internally.
The study was funded by the Lockton Endowment and M. D. Anderson’s pancreatic Specialized Programs of Research Excellence grant.
Conquest - Spring 2007
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