The long-standing focus of our laboratory program involves the radiation and microenvironmental stress response. We are now focusing on """"""""radiation inducible molecular targets"""""""" that is, exploring the use of fractionated radiation to induce a cellular phenotype that makes the cell susceptible for molecular targeted therapy. In essence, radiation would set up the tumor for enhanced drug killing. This project has now demonstrated that different dose sizes of radiation (10 Gy x1, 2 Gy x5 and 1 Gy x10) produce different phenotypes. We have demonstrated that the cells post-radiation are more drug sensitive for at least 1 drug and much more work is in progress but we are now working on combinations of drugs. This work fits into molecular targeted cancer treatment using both the """"""""non-oncogene addiction targets"""""""" and """"""""synthetic lethality"""""""" We have made significant progress in studying the inducible mRNA, miRNA and proteins. We have expanded to add a p53 proficient cell line. Five manuscripts are in now published (Radiation Research Journal) including an overview of the field in Molecular Cancer Therapeutics. Projects now in progress include studying metabolomic changes, in vivo SD and MF for PC3 cells, and exploring epigenetic changes. We are also identifying pathways to target and working on timing of radiation and drug(s). Indirectly related to this work are efforts being done in the Office of the Assistant Secretary for Preparedness and Response in Health and Human Services (HHS). I am heading a group developing civilian medical response planning for radiological and nuclear terrorism and other events. This involves planning, policy, and normal tissue injury-related science. Medical countermeasures are being developed through NIAID support in the Centers for Medical Countermeasures Against Radiation (CMCR). This overall program has major impact to U.S. preparedness and also has a spin-off for normal tissue injury from radiation and the potential for post-exposure mitigators and treatments. We are working with other agencies (NIAID and Dept of Defense) on the potential of bringing these mitigators into cancer care. The critical importance of the NCI- HHS linkage is bringing up-to-date scientficia thinking to medical countermeasure development and diagnosis

National Institute of Health (NIH)
National Cancer Institute (NCI)
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National Cancer Institute Division of Basic Sciences
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Coleman, C Norman; Higgins, Geoff S; Brown, J Martin et al. (2016) Improving the Predictive Value of Preclinical Studies in Support of Radiotherapy Clinical Trials. Clin Cancer Res 22:3138-47
Stone, Helen B; Bernhard, Eric J; Coleman, C Norman et al. (2016) Preclinical Data on Efficacy of 10 Drug-Radiation Combinations: Evaluations, Concerns, and Recommendations. Transl Oncol 9:46-56
Ohri, Nitin; Dawson, Laura A; Krishnan, Sunil et al. (2016) Radiotherapy for Hepatocellular Carcinoma: New Indications and Directions for Future Study. J Natl Cancer Inst 108:
FitzGerald, Thomas J; Bishop-Jodoin, Maryann; Followill, David S et al. (2016) Imaging and Data Acquisition in Clinical Trials for Radiation Therapy. Int J Radiat Oncol Biol Phys 94:404-11
Eke, Iris; Makinde, Adeola Y; Aryankalayil, Molykutty J et al. (2016) Comprehensive molecular tumor profiling in radiation oncology: How it could be used for precision medicine. Cancer Lett 382:118-126
Olson, Adam C; Coleman, C Norman; Hahn, Stephen M et al. (2015) A Roadmap for a New Academic Pathway for Global Radiation Oncology. Int J Radiat Oncol Biol Phys 93:493-6
Petereit, Daniel Grant; Coleman, C Norman (2015) Editorial: ""global challenges in radiation oncology"". Front Oncol 5:103
Grover, Surbhi; Balogun, Onyinye D; Yamoah, Kosj et al. (2015) Training global oncologists: addressing the global cancer control problem. Front Oncol 5:80
Grover, Surbhi; Balogun, Onyinye D; Yamoah, Kosj et al. (2015) Corrigendum: ""Training Global Oncologists: Addressing the Global Cancer Control Problem"". Front Oncol 5:133
Prasanna, Pataje G S; Narayanan, Deepa; Hallett, Kory et al. (2015) Radioprotectors and Radiomitigators for Improving Radiation Therapy: The Small Business Innovation Research (SBIR) Gateway for Accelerating Clinical Translation. Radiat Res 184:235-48

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