This month, I want to focus on the interplay between our intense drive as investigators to understand the root cause of a given disease and the need to identify new treatments.

As basic science researchers, we dig deep to understand the basic mechanisms of a disease, with the idea that such knowledge gives us the best opportunity to devise new drugs for treatment or strategies for prevention. However, this resolute approach can sometimes impede progress.

Andrew von Eschenbach, MD, former director of the National Cancer Institute at the National Institutes for Health, made this case for cancer therapeutics in 2003, and it was not received very well. He related how he gathered an elite group of scientists to discuss cancer biology. The consensus of the group, which included multiple Nobel Laureates, was that we knew too little about basic mechanisms of cancer to undergo major initiatives for new therapies. What Dr. Eschenbach told them was that he wanted to infuse the concept that we should use what we did know about cancer (which was quite a lot) and work with that knowledge to develop novel treatments. As the story goes, he brought the group around to the concept, although many skeptics remained.

A fellow medical resident with me at Washington University, Brian Druker, MD, took this advice to heart. He developed an assay to measure the activity of the mutated BCR-ABL enzyme found in Philadelphia chromosome positive chronic myelogenous leukemia (CML). He screened compounds and discovered imatinib (brand name Gleevec).

Do we understand all the biology behind CML? No. But now, it is treated in a targeted way with this drug, and similar ones, with a very high success rate and few complications. Brian won the Lasker award (and many others) for his discovery. It was a dogged approach to taking what we did know (the unchecked enzyme activity) and pursuing it for a cure.

In our own work, we need to step back from time to time, realize the body of knowledge in our area, and consider how we can leverage it to explore treatment. With today’s high throughput screening techniques and millions of compounds in various libraries, opportunities for discovery may exist that remain unexplored because of our need to know “all things.” We are sometimes our own worst enemies, seeking the holy grail before considering experiments directed towards therapy. We need to lighten up on ourselves.

Stephen Liggett, MD
Associate Vice President for Research, USF Health
Vice Dean for Research, USF Health Morsani College of Medicine
Professor of Medicine, Molecular Pharmacology and Physiology