Research — Radiation Oncology

Dennis Hallahan, MD
4511 Forest Park, Room 202

  1. Radiation Sensitizers: The over arching hypothesis of this research is that interruption of the signaling will improve cancer response to therapy. Inhibitors of these molecular targets are presently in development at pharmaceutical companies. We study the efficacy of specific inhibitors when combined with radiotherapy in mouse models of human cancer.
  2. Radiation Protection of normal tissue: We study the mechanisms of cell death in normal tissues during cancer therapy. In particular, we have found that a signal transduction pathway required for radiation induced apoptosis in normal tissues involves glycogen synthase kinase 3beta. GSK-3beta regulates the apoptosis machinery within normal tissues. Cancer cells do not require GSK-3beta or apoptotic machinery to respond to cancer therapy. In contrast, injuries in normal tissues such as the brain and intestine require GSK-3 signaling. We have found that inhibitors of GSK-3beta prevent injury in normal tissues. These inhibitors prevent injury to the brain and improve neurocognitive function and reduce injury in the intestine of animal models. Presently, we are studying the mechanisms by which GSK-3 inhibition prevents program cell death in normal tissues. We are also studying new drugs intended for clinical trials.
  3. Targeted Drug Delivery to Cancer: We have identified several peptides and over a dozen monoclonal antibodies that bind to cancer following treatment with ionizing radiation. Using this strategy, drug delivery can be targeted specifically to cancer and guided by use of a beam of radiation therapy. These targeting ligands have been conjugated to the drug delivery systems, including liposomes and nanoparticles to improve he specificity of drug delivery of cancer. We collaborate extensively with pharmaceutical companies to target drug delivery to mouse models of human cancer.
  4. Immunotherapy: We characterize the immunological response of antibodies targeted by radiation. These monoclonal antibodies bind to radiation inducible neo-antigens. These antibodies can activate immune response. In addition, therapeutic agents are conjugated to the antibodies to provide cancer specific drug delivery. Identification of radiation inducible neo-antigens involves the co-precipitation of antigens from cancer by use of monoclonal antibodies. Antigens are then identified by use of proteomic technology. Humanization of these mouse monoclonal antibodies is performed with the goal of bringing antibodies into clinical trials. 

Jeff Michalski, MD
Radiation Oncology, Clinical Division
Broad range of opportunities for investigation in:

  1. Prognostic factors and therapy outcome in a variety of patients with cancer
  2. Three-dimensional treatment conformal and intensity-modulated radiation therapy in the treatment of patients with head and neck, lung, pancreas, rectal or prostate cancer.