Anti-Allergy Drug Slows Pancreatic Tumor Growth

Cromolyn, an anti-allergy drug in use for more than 40 years, may be the key to a much-needed treatment advance for pancreatic cancer, considered the most lethal of all cancers.

Researchers at M. D. Anderson found that combining cromolyn with the chemotherapy agent gemcitabine was markedly more effective at retarding the growth of pancreatic tumors in mice than gemcitabine alone. These findings were reported in the December 20 issue of the Journal of the National Cancer Institute.

“Our goal is to offer longer life to these patients, and the combination of these two agents may well do that,” said the study’s lead author, Craig Logsdon, Ph.D., a professor in the Department of Cancer Biology. To date, cromolyn has been used only as a topical agent, so the research team is determining ways to deliver the drug internally.

“Pancreatic cancer is usually refractory to chemotherapy, and the vast majority of patients die from the disease, half of them within six months of diagnosis,” Dr. Logsdon said. “Cromolyn, however, seems to reduce survival mechanisms in pancreatic cancer cells enough to make chemotherapy significantly more effective.”

In this study, pancreatic cancer with the cromolyn-gemcitabine combination grew 85% less than the study’s controls, Dr. Logsdon said. The relationship between how the drug controls allergies and its antitumor effect in pancreatic cancer remains unclear. “It may be possible that cromolyn has more than one target that influences cancer,” he said.

Dr. Logsdon suspects that cromolyn may have antitumor effects in other types of cancer, a theory he is currently testing. “For a basic scientist, this is pretty thrilling,” he said. “In a relatively short time, we have gone from discovering a molecule all the way to preparing for a clinical trial.”

Dual Gene Therapy Suppresses Lung Cancer

Combination gene therapy delivered in lipid-based nanoparticles drastically reduces the number and size of human non-small cell lung cancer tumors in mice, researchers at M. D. Anderson Cancer Center and U.T. Southwestern Medical Center reported in the January 15 edition of Cancer Research.

Given separately, two genes suppressed tumor cell growth, but they had an even more powerful effect when administered together, cutting the average number of tumors per mouse by 75% and the average weight of tumors by 80%.

Combining treatments for a synergistic effect isn’t new in cancer treatment, but combined gene therapy is. “In cancer treatment we have combination chemotherapy, and we also combine different modes of therapy—surgery, radiation, and chemotherapy. Now we’ve got the possibility of combined targeted gene therapy,” said Jack Roth, M.D., a professor in M. D. Anderson’s Department of Thoracic and Cardiovascular Surgery and a senior researcher on the project.

The genes wrapped in the nanoparticles were p53, a well-known tumor-suppressor gene that causes the apoptosis of defective cells and is often shut down or defective in cancer cells, and FUS1, a novel candidate tumor suppressor gene identified in human lung cancer chromosome.

The investigators report that FUS1 works with p53 to force the apoptosis of lung cancer cells because FUS1 suppresses a gene that expresses a protein known to rapidly degrade p53, said senior author Lin Ji, Ph.D., an associate professor in the Department of Thoracic and Cardiovascular Surgery.

Lab experiments first showed that 48 hours after treatment, the gene combination cut the number of viable cells in four lines of human non-small cell lung cancer by 70% to 80% while leaving a control group of normal cells unaffected. In cancer cell lines treated with the gene combination, two to three times more cells underwent apoptosis than in those treated by either gene individually. The research team then confirmed these findings in mouse studies.

“We certainly hope this approach will be more effective than current treatment, but we also think it’s likely to be much less toxic, with fewer side effects, than other types of combined cancer therapy,” Dr. Roth said.

In the first phase of investigations, the FUS1 nanoparticles are being tested alone in a phase I clinical trial at M. D. Anderson for patients with metastatic non-small cell lung cancer.

For more information on this topic or for questions about M. D. Anderson’s treatments, programs, or services, call askMDAnderson at (877) MDA-6789.

Other articles in OncoLog, February 2007 issue:

• New Findings on Aspirin and Heart Attacks
• Kicking Off a Trend: Cancer-Related Deaths Decline
• House Call: Working Out How to Lower Your Risk of Cancer

TOP

Home/Current Issue | Previous Issues | Articles by Topic | Patient Education
About Oncolog | Contact OncoLog | Sign Up for E-mail Alerts

©2008 The University of Texas M. D. Anderson Cancer Center
1515 Holcombe Blvd., Houston, TX 77030
1-877-MDA-6789 (USA) / 1-713-792-3245  
 Patient Referral    Legal Statements    Privacy Policy