Researchers create drug combination that controls both tumor growth and metastasis

Researchers create drug combination that controls both tumor growth and metastasis -

Researchers at UC Davis, University of Massachusetts and Harvard Medical School have created a combination of medications that control both tumor growth and metastasis. By combining a COX-2, similar to Celebrex, and an epoxide hydrolase (sEH) inhibitor, drug control angiogenesis (blood vessel formation), which limits the ability to grow and spread a tumor. The study appears today in the journal Proceedings of the National Academy of Sciences .

"We studied the effects of COX and sEH, both by themselves and in combination, for several years," said lead author and UC Davis Distinguished Professor Bruce Hammock. "We were surprised to find that the dual inhibitor was more active than higher doses of each compound individually or together. by combining the two molecules in one we had a lot more power against several diseases and effects quite unique in terms of growth of the blocking tumor and metastasis. "

COX and sEH enzymes control signaling lipid that has long been associated with inflammation, cell migration, proliferation, hypertension and other processes. COX inhibitors block the production of lipids and inflammatory pain inducing while sEH inhibitors retain antihypertensive, anti-inflammatory and analgesic compounds. COX inhibitors and separate sEH have previously been found to work together to reduce inflammation and neuropathic pain.

After testing inhibitors of COX-2 and sEH individual, the team synthesized the drug (PTUTB), the first COX-2 handset / inhibitor of sEH. They then tested the dual inhibitor against lung and breast human tumors in vitro and in mice. They found that PTUTB blocked angiogenesis, inhibition of the proliferation of endothelial cells, which are essential for formation of blood vessels. This limited steering of tumor growth and metastasis, which reduces the growth of lung tumors, and breast 70 to 83 percent.

In the breast and lung, the dual inhibitor blocked angiogenesis, blocking solid tumor growth, "said hammock." This represents a new blood vessel control mechanism and growth of the tumor. "

Robert Weiss, a co-author and professor of nephrology at UC Davis, added that the combination of drugs obtained results with minimal side effects and no cardiovascular effect or gastrointestinal.

"This is particularly important when administering the COX-2 inhibitors, which have well-known cardiovascular risk," he said. "However, the inhibitor of sEH added appears to block the side of the COX-2 effects. "

research was initiated by the first author Guodong Zhang when he was a postdoctoral fellow in the laboratory Hammock. Zhang previously demonstrated that inhibitors of sEH improve the power of omega-3 fatty acids (fish oil) plans to reduce tumor growth and metastasis, and involved epoxides of DHA dietary supplement as a causative agent.

by advancing a new anti-angiogenic compound, the study extends the work of the famous physician and researcher Judah Folkman at Harvard Medical School, who illuminated the importance of angiogenesis in tumor growth, inspiring a new class of anti-cancer drugs. Two of the authors of the study, Dipak Panigrahy and Mark Kieran, has worked with Folkman at Harvard Medical School.

Although research has focused exclusively on cancer, the researchers said that the double compound could benefit other conditions, such as macular degeneration.

"If we go beyond cancer, this drug combination may block a number of pathologies, ranging from cardiac hypertrophy to neuropathic pain," said Hammock. "The compound seems powerful enough to a number of conditions. "

The search teams are continuing their work on many fronts." a member of our research team has already made more potent inhibitors with more drug-like properties, "said Hammock. "We are looking at the molecules for a variety of indications alone and in combination, including kidney disease, fibrotic diseases, pancreatic and colon cancer and other problems." The molecules are patented by the University of California and are available for licensing and testing.

Co-author Jun-Yan Liu, who conducted analytical chemistry for the study while a doctoral researcher at UC Davis, is examining the effectiveness of the compounds in disease kidney and gout in a laboratory of Shanghai tenth people hospital.

"one of the most exciting things about this project was the ability to work with experts in several areas to find new drugs and new class mechanism that promises to really help people with cancer "said Liu.