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. This work fits into molecular targeted cancer treatment using both the """"""""non-oncogene addiction targets"""""""" and """"""""synthetic lethality"""""""" Over the last year we have made progress in studying the inducible miRNA and proteins. We have expanded to add a p53 proficient cell line. Two manuscripts are in revision (Radiation Research Journal). A proteomics paper is in preparation. Initial studies suggest that cells that survive fractionated radiation are more drug sensitive than the starting cells. 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

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC010670-07
Application #
8349096
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2011
Total Cost
$657,177
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Coleman, C Norman (2017) The Radiation Stress Response: Of the People, By the People and For the People. Radiat Res 187:129-146
Vanpouille-Box, Claire; Alard, Amandine; Aryankalayil, Molykutty J et al. (2017) DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity. Nat Commun 8:15618
Demaria, Sandra; Coleman, C Norman; Formenti, Silvia C (2016) Radiotherapy: Changing the Game in Immunotherapy. Trends Cancer 2:286-294
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
Makinde, Adeola Y; Eke, Iris; Aryankalayil, Molykutty J et al. (2016) Exploiting Gene Expression Kinetics in Conventional Radiotherapy, Hyperfractionation, and Hypofractionation for Targeted Therapy. Semin Radiat Oncol 26:254-60
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:
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
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

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