Allergy Drug Slows Pancreatic Tumor Growth
CancerWise - February 2007
An anti-allergy drug in use for more than 40 years significantly reduced tumor growth in animal models of human pancreatic cancer and increased the effectiveness of standard chemotherapy.
Investigators at M. D. Anderson report that combining the drug cromolyn with the chemotherapy agent gemcitabine was nearly three times better at retarding growth of pancreatic tumors in mice compared to chemotherapy alone.
Significance of results
Researchers say the finding eventually may lead to a treatment advance for patients with pancreatic cancer, believed to be among the most lethal cancers.
Logsdon photo"Our goal is to offer longer life to these patients, and the combination of these two agents may well do that,” says Craig Logsdon, Ph.D., a professor in the Department of Cancer Biology at M. D. Anderson. Logsdon is the study’s lead author.
Logsdon’s team 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 would have two potential drug targets – the secreted protein and the receptor,” he says.
The research team:
- Selected a gene called S100P
- Found S100P over-expression specific to pancreatic cancer
By using gene-silencing techniques, Logsdon discovered that when the protein is disabled, cancer growth is slowed.
He also found that S100P interacts with RAGE, a receptor known to play a role in:
- Alzheimer's disease
When RAGE was blocked in pancreatic cancer cells, addition of synthetic S100P to the tumor did not 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 anti-allergy drugs, including cromolyn. Several members of the S100 gene family did.
Logsdon found cromolyn:
- Bound to S100P
- Slowed tumor growth in laboratory pancreatic cancer cells
- Had a stronger effect when combined with gemcitabine
The study demonstrates that in mouse models of human pancreatic cancer the cromolyn-gemcitabine combination reduced cancer growth by 85% compared to control animals, according to Logsdon.
"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 little effect in patients with pancreatic cancer."
Logsdon is working with physicians at M. D. Anderson to prepare for a clinical trial.
Although cromolyn is widely available as a prescription drug, 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.
Logsdon suspects that cromolyn may have other anti-tumor effects, and he is testing that theory.
MD Anderson resources:
- Pancreatic cancer (American Cancer Society)