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Curtain up

A new drug for pancreatic cancer takes the stage for clinical trials, thanks to the Masonic Cancer Center experts who developed it

What does it take to get to that moment in a clinic when a doctor gives a patient a compound never before used in modern medicine? The story of Minnelide, an investigational drug for pancreatic cancer patients now in a Phase IA clinical trial at the University of Minnesota, illustrates just how complex and exhilarating that journey can be.

“What we did here with Minnelide, we did at the speed of light,” says Gunda Georg, Ph.D., director of the College of Pharmacy’s Institute for Therapeutics Discovery and Development (ITDD) and a member of the Masonic Cancer Center. “Going from drug design to clinical trial in just five years is almost unheard of. Ten years is more typical.”

While Georg played a key role, the Minnelide team stretched across campus and beyond, encompassing laboratory investigators, veterinarians, clinical physicians, attorneys, administrators, philanthropists … the group would need a pretty big stage if they all gathered together.

“Each person has their own core area of expertise,” says Georg, “but bring them all together, and you can do powerful things.”

Ancient mystery

To begin at the true beginning of Minnelide, we’d have to go back hundreds of years to China, where healers used the thunder god vine, or lei gong teng—a perennial vine native to Korea, Japan, and China—to treat rheumatoid arthritis and other autoimmune diseases associated with inflammation.

Flash forward to 1972, when scientists discover that an active compound within the thunder god vine, dubbed triptolide, not only relieves swelling but also stops cell growth in its tracks. They don’t know yet how it works, but it does. So, scientists wonder, could they harness the power of triptolide to stop the growth of cancer cells?

Georg, who holds the Robert Vince Endowed Chair and the McKnight Presidential Chair in Medicinal Chemistry, was brought to the U nine years ago to create the ITDD, a place dedicated to discovering and developing new drug therapies. (She is also a professor and head of the Department of Medicinal Chemistry.)

At that time, the Masonic Cancer Center’s Ashok Saluja, Ph.D., was studying the protein HSP 70 in his lab and had discovered that it helped pancreatic cancer cells grow; with additional investigation, he found that triptolide, an inhibitor of HSP 70, stopped pancreatic cancer cell growth. But his “aha” moment was quickly replaced with another challenge: to turn triptolide into an injectable drug that might help stop the growth of pancreatic cancer cells in humans, it would have to be water-soluble. It wasn’t.

Enter chemist Georg.

“The molecule Dr. Saluja had isolated was basically a grease ball,” Georg explains. “We had to figure out a way to make it both water-soluble and patentable. You can’t invest millions to bring a drug to market without patent rights.”

Georg and her team actually solved the water-soluble challenge in short order and named the new compound “Minnelide” (Minnesota + triptolide). Then it was back to the lab for further study.

Crossing the Ts

Saluja’s findings in the lab—supported by the Eugene C. and Gail V. Sit Chair in Pancreatic and Gastrointestinal Cancer Research, Dr. Robert and Katherine Goodale Pancreatic Cancer Research Fund, and Wellner Family Fund in Pancreatic Cancer Research—were nothing short of amazing. In one mouse study, 21 days of Minnelide treatment made large pancreatic tumors undetectable.

Professional journals published the exciting results, and patients who had pancreatic cancer, which Saluja calls “the worst cancer known,” started lining up to try Minnelide.

But there was still much work to be done. Triptolide, which has to be meticulously isolated from the thunder god vine, is expensive to produce, so the team needed more money to produce a large batch. The U’s Center for Translational Medicine, under the leadership of Masonic Cancer Center member Bruce Blazar, M.D., helped perform these tasks. They also had to modify the drug design to ensure shelf-life stability. Then there were toxicology studies to be done and manufacturing protocols to develop. Across campus, lawyers worked on gaining a patent and then licensing Minnelide.

“The [ITDD] was the lynch pin,” explains Georg, “a place where all the many pieces of the puzzle came together. So in that way, Minnelide is our poster child, proof that this collaborative approach works, and can work quickly.”

Clinical trial

In 2013 it was finally time for hematologist/oncologist Edward Greeno, M.D., to take center stage as he enrolled about 30 people with pancreatic cancer for the Phase IA Minnelide clinical trial conducted at the U and a partner institute in Arizona.

Edward Greeno
Hematologist/oncologist Edward Greeno, M.D., oversees the Phase 1A clinical study of Minnelide. (Photo courtesy of University of Minnesota Health)

 

“It’s been really exciting to get Minnelide into clinical trial,” says Greeno, who is medical director of the Masonic Cancer Clinic and executive medical director of University of Minnesota Health Cancer Care. “We’ve seen tumors shrink at this early stage, so, yes, I think people should be excited about the potential.”

Greeno thanks all of the altruistic people who participate in clinical trials.

“All of these patients have failed every other existing therapy and know they might not get any benefit from the trial, but their participation yields immense benefits to patients who come after them.”

From ancient China to the Masonic Cancer Clinic—you could say that Minnelide has been centuries in the making. But acting in concert, this Masonic Cancer Center team moved quickly to turn hypothesis into reality, basic science into a new drug to be wielded in the war on cancer. Researchers eventually hope to evaluate Minnelide’s efficacy against not only pancreatic cancer but also breast, brain, liver, prostate, and blood cancers.

“This was a natural product that had been used for a long time,” says Georg of triptolide, “and there are many more compounds out there. But which ones should we pursue? Which ones will be viable?

“It all comes down to that collaboration between the different specialties and, for that, the U is one of the best, most comprehensive centers in the country.”