Since the founding of Johns Hopkins University in 1876 commitment to research excellence has been a core virtue. The Department of Radiation Oncology and Molecular Radiation Sciences continues this legacy; holding true to the belief that excellence in research, teaching and patient care are interdependent and not seperate endeavors. The field of radiation oncology has always been a different approach to the treatment of cancer. Our practitioners do not treat patients primarily through drugs or surgery like many other physicians. Instead we are treating cancer with the powerful energy of radiation.

In recent years there have been staggering advances in molecular-based technologies that have affected the field of radiation oncology in ways only dreamed of before. Using molecular-based imaging, we are be able to see tumors like never before. Not only what is in the organ being examined, but in the cells related to the tumor outside the organ. We are also able to see the function of the tumor and direct therapies specifically toward it. Radiation causes damage to a cell's DNA, the critical molecule of life for animals and the individual cells of which they are comprised. Evolution has armed us with many different proteins whose sole function is to make sure

that the genome (which is made up of long strands of DNA molecules) remains in an undamaged state.

Either they can repair the damaged DNA better than normal cells can and/or they can survive with many alterations to their genomes. This causes a problem for many radiotherapy treatments, where the radiation given to the patient is more efficient at killing their normal, non-cancerous, cells than it is the actual cancer. Tumors respond to radiation in different ways. If a tumor depends on a specific protein to repair its DNA then we might be able to deliver the radiation in such a way that avoids activating this DNA repair system. Certain tumors use this repair pathway to greater advantage than others, therefore, hundreds of different cell lines are tested in our research projects in order to develop alternative treatment options.

We are now studying some of these alternatives and have made some very interesting observations. Likewise, there are certain drugs that target these DNA repair pathways that can be designed to seek out only the cancer cell and when combined with radiation destroy cells at a greater rate. We've designed several ways to get the drugs into those pathways, one of the most interesting being through common cold viruses called adenoviruses. By injecting the virus into the tumor being irradiated it has been shown both in culture dish and in animals growing tumors that this

combination will kill seven times more cells with the same dose of radiation than with radiation alone. Clinical trials are about to start based on this work. Work in our laboratory aims at developing new gene therapy approaches that can reduce the amount of these repair proteins in the tumor cells, but leave the normal cells untouched. Now the cancer cells are made sensitive to the radiation treatments and the effectiveness of the radiotherapy is increased i.e. we can kill more cancer cells with less total radiation given to the patient, which we hope will reduce any unwanted side-effects which may be associated with radiation treatment.

Preliminary work within our laboratory has produced encouraging results. We can treat cultured cancer cells with gene therapies that we have developed and kill up to 3 times more cells than if we leave them untreated. We are now developing ways to improve on these initial findings and envisage that such an approach could dramatically improve the effectiveness of a course of radiotherapy. Our expectations for excellence in research is at an all time high, and we are finding new ways to direct subatomic particles precisely at tumors. This allows us to evlove in ways that achieve our ultimate goals of translating what we do in research into our clinical practices and improving the lives of our patients.