POP: "Translational research" is a buzzword these days. What does it really mean?
Nadler: Most of the research supported by the National Institutes of Health and other funding agencies investigates how cells work. These studies are conducted in many species, from yeast to flies to fish to mice. The discoveries made in these basic experiments must somehow find their way to human experiments to try and help cancer patients or prevent the disease in those at risk. That's what translational research is all about.
For example, a discovery by Dana-Farber scientists could identify a target in cancer cells that a pharmaceutical company uses to make a new drug, and we could conduct that clinical trial focusing on whether the drug hits the right target. But it could also mean that a pharmaceutical company brings a novel experimental drug to DFCI for testing in clinical trials. Again, we would not just conduct the trial but, more importantly, investigate whether the drug hits the right target. A translational investigator must attempt to understand why a clinical experiment succeeded or failed.
"We will measure whether our translational approaches change the standard of practice in oncology to ease suffering and save more lives."
— Lee Nadler, MD
POP: Dana-Farber is a longtime leader in cancer research. Are discoveries made here being translated into new therapies on a regular basis?
Nadler: We know how to do science brilliantly here. We get an "A" in research, and now we also get an "A" in clinical care, but we don't do as well in translational research — and neither does any other cancer center. The time from a discovery to a new therapy is just too long. Our goal must be to overcome the obstacles.
For one thing, this kind of research requires teamwork and collaboration, yet the academic system doesn't normally reward teamwork; it values research by individuals. Translation requires a diverse team that includes bench scientists, multidisciplinary clinicians, clinical investigators, statisticians, nurses, and data managers. Although most bench scientists fervently support the translation of their basic studies, they are reluctant to execute these translational experiments in their own laboratories; they must use their limited, precious space to make basic breakthroughs.
The Institute's infrastructure and focus are not as well-developed as they could be to foster translational research. We need to provide an environment and culture that encourages both human disease-oriented laboratory research and clinical studies that apply these findings to patients. We have now embraced the term "impact" as one of Dana-Farber's core values; to achieve impact, you must have translation.
Still, the Institute has had some striking successes in the early development of drugs. For example, the drug PS-341 that has shown effectiveness in multiple myeloma was developed in a laboratory here in collaboration with a pharmaceutical company.
Nadler: Yes, that's true. Ken Anderson, MD, the new chief of Hematological Malignancies Research at Dana-Farber, and his colleagues have created the premier translational myeloma program in the world. Without question, some researchers have attracted donor and government funding and have had brilliant success. But we want to level the playing field for all; it's about building translational research into the institutional culture.
What are some other examples of successful translational developments at Dana-Farber?
Translational researchers in the laboratory of Kenneth Anderson, MD (center), include (clockwise, from bottom left) Edie Weller, PhD; Kathleen Kelly, RN, BSN; Laurence Catley, MD; Constantine Mitsiades, MD, PhD; Teru Hideshima, MD, PhD; Richard Leblanc, MD; Paul Richardson, MD; Tania Shepard; and Reggie Deocampo.
Nadler: The best example in 2002 is the finding that the drug Gleevec can lead to major remissions in a cancer called GIST (gastrointestinal stromal tumor). This is a type of sarcoma that until now did not respond to any form of conventional treatment.
The seminal idea was developed several years ago by a team working at Dana-Farber, linking the laboratory and clinic. Drs. David Tuveson, George Demetri, and Jonathan Fletcher reasoned that Gleevec, a drug that had already been approved for treating chronic myelogenous leukemia (CML), might hit another molecular target other than the Abelson kinase in CML.
This team involved other DFCI researchers, including Jim Griffin, and they conceived a set of laboratory experiments to see if the drug would be effective against GIST. The experiment worked. Demetri, a sarcoma expert in Medical Oncology, immediately saw the translational potential of this effort. This trial had tremendous impact; it helped spur the U.S. Food and Drug Administration to approve Gleevec for widespread distribution and use against GIST, and many patients who faced certain death from this rare stomach cancer saw their tumors shrink dramatically. This changed the standard of care for these patients immediately.
We have witnessed many other bench-to-bedside experiments over the past 30 years at Dana-Farber. We can be proud of the advent of monoclonal antibody diagnosis and therapy, novel types of bone marrow transplantation for liquid and solid tumors, applications of cytokines in the treatment of cancer, development of potential cancer vaccines, and, more recently, new small molecule therapies in hematologic malignancies and solid tumors. We have a strong history, but we haven't reached our full potential.
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