A number of agents have begun testing for this project. One agent, a MEK inhibitor, has been evaluated as a radiation sensitizer both in vitro and in vivo. The agent was found to sensitize three histologies to radiation in vitro and to sensitize two tested cell lines to radiation in subcutaneous xenografts. Additional mechanistic work has revealed that the cause of this senstization appears to be related to abrogation of the G2 checkpoint after irradiation. Additional work with this compound is focusing on possible biomarkers of effect to identify candidate markers of efficacy for clinical translation. In addition, the agent was comined with chemotherapy and additional sensitization to radiation was seen, supporting the conduct of a clinical trial. A clinical trial has recently been initiated with this compound with myself as the Pricipal Investigator. Two additional agents are currently undergoing testing for efficacy as radiation sensitizers. These include a small molecule poly(ADP-ribose) polymerase (PARP) inhibitor and a multi-target tyrosine kinase inhibitor. The preliminary in vitro clonogenic assays have been promising for these two compounds. Additional in vitro work, in vivo work, and mechanistic work will be ongoing. The eventual goal for these compounds is clinical translation into trials as radiation sensitizers. In additon, the PI has been active in translating findings from collaborators in the Radiation Biology Branch inot clinical trials.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Investigator-Initiated Intramural Research Projects (ZIA)
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National Cancer Institute Division of Basic Sciences
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Citrin, Deborah; Hudak, Kathryn; Camphausen, Kevin A (2013) Biomarkers to guide therapy or surveillance for prostate cancer. Biomark Med 7:827-9
Citrin, Deborah; Camphausen, Kevin A (2013) Biomarkers for prostate cancer: who will benefit from local treatment, who harbors occult systemic disease and who needs treatment at all? Biomark Med 7:823-5
Urick, Mary Ellen; Chung, Eun Joo; Shield 3rd, William P et al. (2011) Enhancement of 5-fluorouracil-induced in vitro and in vivo radiosensitization with MEK inhibition. Clin Cancer Res 17:5038-47
Kelly, Ronan J; Lopez-Chavez, Ariel; Citrin, Deborah et al. (2011) Impacting tumor cell-fate by targeting the inhibitor of apoptosis protein survivin. Mol Cancer 10:35
Citrin, Deborah; Camphausen, Kevin; Wood, Bradford J et al. (2010) A pilot feasibility study of TNFeradeā„¢ biologic with capecitabine and radiation therapy followed by surgical resection for the treatment of rectal cancer. Oncology 79:382-8
Mitchell, James B; Choudhuri, Rajani; Fabre, Kristin et al. (2010) In vitro and in vivo radiation sensitization of human tumor cells by a novel checkpoint kinase inhibitor, AZD7762. Clin Cancer Res 16:2076-84
Chung, Eun Joo; Brown, Aaron P; Asano, Hiroaki et al. (2009) In vitro and in vivo radiosensitization with AZD6244 (ARRY-142886), an inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 kinase. Clin Cancer Res 15:3050-7
Brown, Aaron P; Wendler, David S; Camphausen, Kevin A et al. (2008) Performing nondiagnostic research biopsies in irradiated tissue: a review of scientific, clinical, and ethical considerations. J Clin Oncol 26:3987-94