BRIDGE - BUILDER :
DeWeese New Head of Radiation Oncology

Imagine looking at something—say, a garden— through two different lenses. One lens zooms in so much that you can focus on a single weed; the other gives you an aerial shot. This is how Theodore L. DeWeese, M.D., works on prostate cancer. He deals with the very small—cancer on a molecular level, in viral gene therapy studies with urologist Ron Rodriguez, and work on oxidative damage with oncologist Bill Nelson—and the bigger picture—pulling together teams of physicians and scientists, tailoring specific therapy for individual patients, and working with surgeons and oncologists to design new treatment combinations.

DeWeese is recognized internationally for his expertise in the molecular aspects of radiation’s interaction with human cells, particularly prostate cancer cells. He also has designed systems to deliver droplets of cancer-killing viruses—highly precise computer programs that place tiny doses of virus or radiation at exact intervals within the prostate, guided by transrectal ultrasound and CT imaging. But at Hopkins, he is also renowned for his ability to make multidisciplinary collaborations work—so much so, that he has been named the first director of the new Department of Radiation Oncology and Molecular Radiation Sciences.

He is a bridge-builder: Leader of a National Cancer Institute Specialized Program of Research Excellence (SPORE) “translational science” project—turning ideas developed in the laboratory into new forms of treatment for patients, and leader of a Department of Defense Cancer Consortium grant project in adenoviral gene therapy (working with Rodriguez - click here for details ).

“The treatment of prostate cancer has evolved, so that no one specialty has ‘ownership’ of it any more,” says Patrick C. Walsh, M.D.. “Because the disease comes in so many different forms, there will never be a single standard way to beat it; we need many options, and many scientific minds from different disciplines turned to the problem. Ted exemplifies this team approach beautifully. Both Hopkins and our patients are very lucky to have him as our leader.”

DeWeese is excited about the possibilities of his new job, he says. “We will be nearly doubling our faculty—from 12 to 23—over the next three years, and tripling our lab space.” One of those new faculty members is radiation oncologist Danny Y. Song, M.D., who will “re-establish and lead our prostate brachytherapy effort as well as participate in the management of other patients with genitourinary malignancies, and patients with lung cancer.” Song will also lead the prostate cancer clinical research program.

DeWeese is creating a new division of medical physics, bringing in Ph.D. scientists who can apply physics and mathematics expertise to a host of questions. For example: “What does it mean for the patient when a specific gene is functional or not functional, and how can this help us design a better radiation strategy? We tend to treat everybody the same,” says DeWeese. “But if you could genetically ‘type’ a man with prostate cancer, you could individualize that man’s therapy far more than we do today.”

DeWeese hopes to be able to generate an instantaneous report card that tells him how well radiation is working in a patient, “in a real-time fashion, what this is doing to the tumor. But almost as importantly, can we also monitor the normal tissues that happen to be getting radiation also? Which patients’ rectums are more sensitive than others’? If the normal tissue is not being affected, we could give more radiation. If it is being harmed, we could cut back, or come up with another approach.”

With the goal of nearly instantaneous feedback from a PET or other nuclear medicine scan, DeWeese and colleagues are testing molecular markers, and working to develop them into a clinical trial—which would be the first of its kind.

In other research, DeWeese and colleagues are studying how cells recover from radiation damage. “We don’t want a cancer cell to repair damage; we want to kill it,” he explains. Cells have specific sensors that sound the alarm that there has been damage, and call for genetic repair crews. “Those sensors are like the cell’s radar,” he says. “They constantly scan the cell. If it’s injured, the sensor sees it, and starts a whole cascade of events to repair the damage.” If those sensors can be disabled—and this can happen, DeWeese found out, by preventing a certain protein from being made—then the damage doesn’t get reported. And this means that radiation and chemotherapy can kill more cancer cells at lower doses.