From Mice to Men

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Paulson and Prabhu have cured leukemia in mice, but the most important question remains: Will the therapy work in humans?

“The results are very promising,” said Thomas Loughran, director of the Penn State Hershey Cancer Institute and an expert on leukemia, “but there is still much more work to do.”

Loughran said making the jump from mice to humans requires multiple time-consuming steps and about $1 billion.

“Before a cancer therapy can begin clinical trials, it must go through a preclinical development phase,” he said. “This includes testing the therapy in culture to see if it works on human cancer cells and then testing to see if it works in larger animals, such as pigs, dogs, and nonhuman primates. If the therapy works safely in these animals, the researchers must get approval from the FDA [U.S. Food and Drug Administration] to begin clinical trials. The FDA wants to make sure the therapy makes perfect sense before it allows scientists to test it in humans.”

Once the FDA has approved the therapy, the three phases of clinical trials can begin.

“In phase I, you give a low dose of the medication to three or four patients,” Loughran said, noting that these patients typically are volunteers who have relapsed and are seeking a new medication that might help them. “If there are no side effects, you increase the dose. Once you find the maximum safe dose for patients, you move into phase II of clinical trials.”

Phase II includes giving the maximum safe dose to a larger number of patients, typically about 30 people.

“The goal here is to further examine the drug’s safety and effectiveness,” he said.

Phase III includes a randomized study in which some patients are given the drug while others are given the best standard therapy. Neither the doctor nor the patient knows who has received the drug. Such a study usually includes hundreds or thousands of patients.

“If the new medicine significantly improves survival or remission rates among patients, then the FDA will set up a panel to vote on whether the data is valid and whether the medicine merits becoming commercially available,” Loughran said.

Loughran explains that Paulson and Prabhu’s J3 compound will have to go through all of these steps before it can be sold as a drug. And because the scientists are relatively poor university researchers compared to industry researchers, the team will have to attract industry support to move through the clinical-trial process.

Loughran’s own research, some of which he conducts in collaboration with Paulson, also involves the development of leukemia therapies. The first discoverer of large granular lymphocytic (LGL) leukemia, a chronic but rare form of leukemia, Loughran currently is seeking a therapy that targets cancer cells among LGL patients rather than “assaulting their entire bodies the way chemotherapy does.”

“Curing cancer in humans is an expensive, time-consuming endeavor requiring a significant amount of interdisciplinary collaboration,” Loughran said. “But it’s worth it. I see patients every day who are suffering from leukemia. They are our parents, our children, our friends, and our neighbors. We need to do all that we can to help improve their outcomes.”