Novel Molecular Targets for Tumor Radiosensitization Molecular Radiation Biology and Oncology Workshop: Translation of Molecular Mechanisms Into Clinical Radiotherapy Kristoffer Valerie, Ph.D., 1 * Anatoly Dritschilo, M.D., 2 Gillies McKenna, M.D., 3 and Rupert K. Schmidt-Ullrich, M.D. 1 1 Department of Radiation Oncology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 2 Department of Radiation Medicine, Georgetown University Medical Center, Washington, District of Columbia 3 Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania INTRODUCTION A scientific workshop sponsored by the Radiation Effects Branch of the National Cancer Institute was held March 8 and 9, 1999, in Rockville, Maryland. To promote scientific collaborations and the ex- change of new technologies, the workshop brought together investigators from three geographically close medical centers that recently were awarded P01 grants in radiation oncology to explore new avenues of translating novel molecular mechanisms of cellular radiosensitization into clinical trials. Sci- entists from Georgetown University (GU), Medical College of Virginia (MCV), and University of Pennsylvania (UP) presented their work in four sci- entific sessions followed by general discussions. Dr. Kristoffer Valerie (MCV), scientific coorga- nizer with Dr. Rupert Schmidt-Ullrich (MCV), opened the workshop by welcoming everyone. SESSION I: CELL PROLIFERATION RESPONSES AND RADIORESISTANCE Dr. Ruth Muschel (UP) chaired Session I and also gave the first presentation, “The Mechanism of Ra- diation Induced G2 Block and Its Relationship to Radiosensitivity.” Dr. Muschel’s studies on the molecular factors affecting the G2 delay have shown that the G2 delay induced by radiation has a multicomponent effect involving altered cyclin B expression, CDC2 kinase activation, and cellular localization. She has expanded her studies on drugs in conjunction with radiation and induction of G2 delay, in particularly in response to different eto- poside agents. Dr. Muschel presented data demon- strating that the Cyclin B/Cdk2 complex is inhib- ited by the phosphatase Cdc25 through the cell cycle checkpoint protein Chk-1 and that radiation results in a decrease of CyclinB/Cdk2 histone H1 kinase activity. Inducible expression of Cyclin B1 demonstrated that increased levels of Cyclin B1 do not alter cell cycle progression at lower doses of 2 to 4 Gy, but abrogate the G2 delay after larger doses. Furthermore, p34 cdc2 is excluded from the nucleus after Cyclin B1 induction and irradiation with 3 Gy. In studies on the mechanisms underly- ing the G2 delay in collaboration with Dr. Timothy Yen (UP), she has cloned several human homologs of the chk-1 gene, which have not been previously identified. She has developed specific antibodies to Contract grant sponsor: National Cancer Institute; Contract grant numbers: P01CA72955, P01CA74175, and P01CA75138. *Correspondence to: Kristoffer Valerie, Ph.D., Department of Radiation Oncology, Medical College of Virginia, Virginia Commonwealth University, 401 College Street, Box 980058 Richmond, VA 23298-0058. Phone: (804) 225-3288; Fax: (804) 828-6042; E-mail: kvalerie@hsc.vcu.edu Received 16 August 1999; Revised 21 September 1999; Accepted 21 September 1999 Int. J. Cancer (Radiat. Oncol. Invest): 90, 51–58 (2000) © 2000 Wiley-Liss, Inc. Publication of the International Union Against Cancer