From old drugs, new cancer treatments

When it comes to finding better drugs for cancer, Dana-Farber oncologist Dr. David Frank is not a patient man. While new cancer science promises to bring novel, improved therapies to the bedside, it can take many years — and Frank isn’t willing to wait.

“We need to get new treatments to patients as soon as possible,” he says.

In his lab, Frank studies the broken pathways in cancer cells that drive them to the uncontrolled growth that forms tumors. In a number of cancers, one of these pathways, called STAT3, is like a switch that’s stuck in the “on” position. Blocking or disabling that broken switch is a logical strategy to derail the cancer.

David Frank, MD, PhD, in his lab at Dana-Farber
David Frank, MD, PhD

Scientists at Dana-Farber and elsewhere are hard at work looking for compounds that can hit “targets” like the malfunctioning STAT3 pathway. But even if they find one, it could take 10 years — and hundreds of millions of dollars — for a pharmaceutical company to turn it into a drug. And then the price would likely be very high.

Frank had an idea for shortcutting the process — a bit of a gamble, but worth trying.

Sometimes, drugs already approved by the U.S. Food and Drug Administration (FDA) for one medical condition turn out to be effective for a different condition as well. If an approved drug could be found that blocked the STAT3 pathway, Frank reasoned, it could quickly be re-purposed for treating cancer.

Thanks to support from the Multiple Myeloma Research Foundation, Frank had access to a library of 1,200 samples of drugs that were previously FDA-approved. Moreover, the drugs were no longer protected by patents, “so there would be no companies with which you would have to negotiate rights,” Frank explained.

The library arrived at Dana-Farber in the form of 15 laboratory plates, each containing 80 different drug samples.

After six months of screening and analysis, one drug stood out. Called pyrimethamine, it’s widely used to treat malaria and other parasitic infections — though not by inhibiting the STAT3 pathway, which isn’t found in those parasites.

“We found that it was also very effective in blocking the growth of cancer cells, and relatively non-toxic,” says Frank.

So in a matter of months, the screening strategy yielded a “new” old drug for cancer. Since pyrimethamine has been proved safe for humans, it can go into clinical trials almost immediately.

Frank and Dr. Jennifer Brown, who specializes in chronic lymphocytic leukemia and is the director of Dana-Farber’s Chronic Lymphocytic Leukemia Center, began a clinical trial of pyrimethamine for patients with chronic lymphocytic leukemia.

Funded by the Lymphoma Research Foundation, the trial is now recruiting patients. If the drug proves effective, says Frank, it shouldn’t be difficult to make it available as an “off-label” use. And it’s much cheaper than the cost of a newly developed cancer drug would be.

Frank says he’s “very satisfied” with how the gamble paid off.