Mayo Magazine

Existing Drug, New Treatment?
Mayo Researchers Test Arthritis Drug as Lung Cancer Treatment

This cancer research team at Mayo Clinic Jacksonville has recently discovered a potential new therapy for non-small cell lung cancer, the leading cause of cancer-related deaths in the United States. From left to right: Erin Donivan, Capella Weems, Lee Jamieson, Ph.D., Alan Fields, Ph.D., Melody Stallings-Mann, Ph.D., and Roderick Regala, Ph.D.

When Alan P. Fields, Ph.D., arrived at Mayo Clinic Jacksonville three years ago to direct the laboratory research program in cancer, he talked about the possibilities Mayo offered for advancing his research. Today, he already has an inspiring example: a potential new therapy for non-small cell lung cancer (NSCLC), the leading cause of cancer-related death in the United States.

The therapy is Myochrysine (aurothiomalate), an arthritis drug already approved by the Food and Drug Administration (FDA). Mayo is now planning the first clinical trial to test the arthritis drug as a lung cancer treatment. In pre-clinical studies, Dr. Fields' team demonstrated that the drug blocks the growth of NSCLC tumors. If clinical trials yield similar results, the drug will be used with other therapies to combat NSCLC.

From Bench to Bedside

The initial phase of clinical trials will determine dosage levels for patients with NSCLC. If subsequent phases show Myochrysine has benefits, it could help the estimated 170,000 people who are diagnosed each year with lung cancer. In more than 85 percent of these cases, the diagnosis is some form of NSCLC.

Dr. Fields' work completes a remarkable chain of events that began before he joined Mayo. A cancer cell biologist, he came to Mayo from the University of Texas Medical Branch, where he and a group of colleagues produced findings about a family of proteins, called protein kinase C, and its connections to colon cancer.

The more Dr. Fields learned about these proteins, the more it became clear that they play key roles in many types of cancer, including lung cancer. While at Texas, he produced evidence linking lung cancer and one particular form of protein kinase C, called protein kinase C iota (PKC iota). The chance to more fully explore this link lured him to Mayo Clinic, accompanied by several of his Texas colleagues.

A Good Move

Once at Mayo Clinic Jacksonville, Dr. Fields and his team collaborated with Mayo colleagues to discover PKC iota's role in lung cancer. The results have potentially far-reaching implications for cancer research.

The team showed that the protein has a powerful role in NSCLC. It's overly abundant in lung tumors, and its presence may predict a cancer's aggressiveness and likelihood of responding to treatment. Furthermore, the team discovered the protein is altered during the early stages of the cancer process and in its altered form it drives growth of tumors by binding to another protein, Par6.

Armed with that information, the team screened nearly 1,000 FDA-approved medications to determine if any could block binding of PKC iota to Par6. They discovered several possibilities, the most promising being Myochrysine.

Two scientific milestones also have emerged from this work. Dr. Fields' group is the first to show a link between this protein and cancer. In addition, their work is the first to show a new approach for cancer therapies — to combat the disease by blocking cancer-promoting signals between proteins.

"When we arrived at Mayo, we had an idea of what we might discover, but we needed to expand our studies to confirm our hypothesis," says Dr. Fields. "By coming here, we accessed a much larger bank of tissue samples, both cancerous and noncancerous, as well as clinical data on the patients who donated those samples. This was crucial to demonstrate that PKC iota was an important new drug target. Coming to Mayo also enabled us to pull together the interdisciplinary team required to conduct a clinical trial. Mayo really is unique because it creates an environment that enables researchers and clinicians to collaborate very effectively."

A Sound Philanthropic Investment

Philanthropy had a prominent role in creating this opportunity. The exploratory phases of the research were funded through an annual research budget Mayo provided to Dr. Fields. Nearly 75 percent of these funds came from gifts from benefactors who have designated their support for cancer research. These funds are vital for pursuing novel high-risk and high-reward research ideas, which are often difficult to fund through the National Institutes of Health and other sources, because these agencies prefer to fund more established projects.

With this support, Dr. Fields' team performed studies that span the medical research spectrum and illustrate Mayo's collaborative approach to research. Staff members in his lab worked with colleagues at Mayo Clinic Rochester to evaluate more than 300 lung-tissue samples and perform statistical analyses to validate the significance of their protein target. They also collaborated with Christopher Eckman, Ph.D., a neuroscientist at the Jacksonville campus, to design the test that eventually identified Myochrysine as their new treatment candidate. Benefactor funds will help Mayo launch the first clinical trial of this new therapy.

In funding these activities, benefactors have made an excellent investment in research, says Scott Kaufmann, M.D., Ph.D., an oncologist who consulted on the clinical trial design. "We don't know if the drug will help people with lung cancer, but there is tremendous interest right now in identifying pathways that contribute to cancer and developing therapies that target these pathways, just as Alan has done."

Another measure of the value of philanthropic support is whether it helps investigators secure funding from outside agencies to continue the research. That, too, has occurred for Dr. Fields and his team. They have received three grants totaling $2 million to continue the research, including a $1 million grant from the state of Florida. The team will use the funding to see if smoking causes lung cancer through the same mechanism Dr. Fields' team has identified.

Regardless of what happens, one thing is clear: Dr. Fields won't rest on his accomplishments. Even if the clinical trials go well, they will represent only an initial step, he says.

"In many respects, a clinical trial is one of the final steps in translating a basic science discovery into a new treatment," he says. "But in some ways, it's only the first step because we'll use the information we gain to refine our knowledge and seek even more effective treatments."