Sign Up for Fundamentals

Stay up-to-date with the latest research findings from the Institute for Basic Biomedical Sciences.

Please enter a valid email address.
Fundamentals Topics+

Dung Le on the Hard Work Behind a Historic Drug Approval


More Profiles

Dung Le on the Hard Work Behind a Historic Drug Approval

Interviewed by Shawna Williams

Dung Le on the Hard Work Behind a Historic Drug Approval
Dung Le is an associate professor of oncology at the Johns Hopkins University School of Medicine and member of the Johns Hopkins Bloomberg~Kimmel Institute. She co-led a clinical trial that was instrumental in the Food and Drug Administration’s recent approval of the drug pembrolizumab to treat cancers based on their genetic characteristics.

What sparked your interest in science and medicine?

Le: I've always been scientifically inclined, and knew growing up that I wanted to be a doctor and apply science to patients. In medical school, I realized I needed to really understand science to be able to apply it to better helping patients.

 What are your research interests?

Le: Most of the research I do is translational—specifically, applying basic science knowledge to clinical trials. I partner with scientists like Luis Diaz, Bert Vogelstein, and Elizabeth Jaffee, and translate what's being done in their labs to patients. We're not going to understand how to move treatment forward without understanding mechanisms. We now know that cancer is thousands of diseases instead of one, so effective treatment hinges on identifying the right molecular targets in each cancer, and the patients who can benefit from a particular drug.

And how did you get involved with the pembrolizumab trial?

Le: During the first Hopkins clinical trial of a drug called a PD-1 inhibitor, there was the observation that only one colon cancer patient responded. Based on conversations with Bert Vogelstein, Ken Kinzler, and Luis Diaz, the investigators thought maybe it was because that patient had a mismatch repair mutation, which would give the tumor more mutations than most cancers and make it easier for the immune system to detect. They wanted someone on the immunological side—me--to help design a trial to see if the drug could work for others with the same type of cancer-causing mutation. When we were designing the trial, we thought that if mismatch repair mutations really are a marker indicating pembrolizumab could be effective for these types of patients, that marker should apply to all cancers, not just colon. There were these common themes in different kinds of tumors. That’s what led us to this study, which confirmed that idea.

What do you see as most significant about the FDA’s approval of pembrolizumab for new uses?

Le: It’s really unprecedented. All cancer therapies until now have been based on tumor of origin histologies—this is the first time a drug has been approved for use based on a biomarker. That biomarker is only found in about 4 percent of cancers, but this actually adds up to a substantial number of patients.

What are the next steps for this research?

Le: The next step for mismatch repair-based therapies is confirmatory studies with longer follow-up. The studies we’ve done were in patients with advanced cancers for whom other therapies had failed. We plan to look at whether pembrolizumab is also effective in patients at earlier time points, as a first-line treatment. Others are also testing whether similar agents are effective for those whose cancers have been removed but who have a high risk for recurrence. 

What’s your advice for aspiring physician scientists?

Le: I’ve always kept the patient in mind at the other end of my research. Even though it's a long journey, the reward is that if you can really understand the biology, what you're doing in the lab will eventually translate into someone’s day-to-day life. Sometimes you can get lost in the day-to-day of lab, but each piece of knowledge gained is important for patients.