RADIATION AND CELLULAR STRESS RESPONSE

PROGRAM LEADERS

	Nancy L. Oleinick, PhD Professor, Radiation Oncology nlo@case.edu
	Alexandru Almasan, PhD Associate Professor, Cancer Biology, Radiation Oncology almasaa@ccf.org
	Timothy J. Kinsella, MD Professor, Radation Oncology tjk4@case.edu

Program Themes | Program Information | Program Members

PROGRAM THEMES

• To promote photochemical, cellular, animal tumor, and clinical research into photodynamic therapy with Pc 4 and related photosensitizers to improve cancer therapeutic strategies using PDT.
• To investigate signaling of cellular stress responses by DNA damage that lead to apoptosis or growth arrest, and mechanisms of protection, in order to develop novel approaches for reducing cancer incidence and improving treatment.
• To explore mechanisms of mismatch repair and base-excision repair of DNA and their modification to promote pre-clinical and clinical studies of modifying agents developed within this program.

PROGRAM INFORMATION

The major scientific focus of this Program is on the mechanisms of responses of cells to radiations, both ionizing and non-ionizing, and related cellular stresses. The program encompasses three scientific foci: Photodynamic Therapy, Cellular Stress Responses, and DNA Damage and Repair. The scientific themes of this program are all directed to understanding how cancer cells respond to ionizing or non-ionizing radiation or related physical or chemical stresses, such as hypoxia or reactive oxygen species. The majority of the members of this program have dedicated their research efforts to the study of cancer, and more particularly, the treatment of cancer. All of the work in the Photodynamic Therapy (PDT) focus is directed to improving this unique cancer treatment. A novel photosensitizer, Pc 4, has been developed in this focus area and is now in clinical trial. Studies in the Oxidative Stress Response focus are mainly on the signaling responses of cancer cells, although other relevant model systems are used where they can facilitate understanding of pathways. An innovative radioprotector, PFT-u, has resulted from the work in this focus area and is in late-stage preclinical development. The research in the DNA Damage and Repair focus is entirely directed to elucidating mechanisms of DNA damage by radiation and other oxidative damage-producing cancer therapies, the role of DNA repair in determining the sensitivity of cancer cells to treatment, and developing these discoveries into new cancer treatments. Two new therapeutics, the prodrug IPdR as a radiosensitizer and methoxyamine (MX), a small molecule inhibitor of base excision repair, have evolved from this focus and are now in clinical trials. Each of the focus areas has developed a set of activities that emerge from and cross-fertilize the research interests of the individual members.

PROGRAM MEMBERS