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ETS Gene Fusions as Predictive Biomarkers of Resistance to Radiation Therapy for Prostate Cancer

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Technical Report,15 Jul 2010,14 Feb 2016

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University of Michigan Ann Arbor United States

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The research goals of this grant proposal are to 1 investigate the effect of ETS gene fusions on radiation phenotype in preclinical models of prostate cancer, 2 to explore the mechanism of interaction between ERG the predominant ETS gene fusion product and the DNA repair protein DNA-PK, and 3 to determine if ETS gene fusion status is a clinical biomarker of radioresistance for prostate cancer. The training goals of this grant proposal included a series of regular meetings with mentors, research seminars, journal clubs, and workshops, all of which are intended to help Dr. Feng develop as a translational scientist. This grant proposal was approved as a five-year award this report summarizes accomplishments over the entire period of the grant, from July 15, 2010 to February 28, 2016. Overall, this grant effort has been very successful. The work accomplished as a result of this grant resulted in seven publications in very high-impact journals, five presentations, and five grants three from the Prostate Cancer Foundation, one from Celgene, and one from the Fund for Cancer Research. Additionally, Dr. Feng has met the training achievements specified in his original grant. The research proposed in this training grant represents an important area within the field of prostate cancer research. Because ETS gene fusions are thought to be driver alterations in over half of all prostate cancers, understanding the mechanistic and potential clinical implications of these gene fusions has significant ramifications, particularly in the context of radiation therapy, which represents a primary treatment modality for localized prostate cancer. We have accomplished 17 out of 17 proposed subtasks, as defined in the revised statement of work approved in 2015. Our work has helped define the functional significance of the interaction between ETS gene fusions and DNAPK inhibition, and has established this axis as a potential therapeutic target.

Subject Categories:

  • Radiobiology
  • Genetic Engineering and Molecular Biology
  • Biochemistry

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