This Leadership Application in Chemoprevention complements my U01 Research application that has been submitted for its third renewal to the MMHCC. My proposed U01 research will integrate analyses of our unique mouse models of prostate cancer with analyses of human prostate cancer using state-of-the-art systems biology approaches to define an """"""""interactome"""""""" of mouse and human prostate cancer;the ultimate goal will be to identify new druggable targets for advanced prostate cancer and to evaluate the efficacy of such targets for therapeutic intervention. Although my U01 MMHCC research application is focused on cancer progression and advanced disease, I am highly committed to the effective utilization of mouse models for studying cancer initiation, early detection, and prevention. Indeed, despite many recent advances in the design and demonstrated relevance of GEM models for human cancer, GEM models are vastly underutilized in cancer prevention research. In my view, this reflects the need for improved communication among investigators across many disciplines, and particularly in the areas of mouse modeling and cancer prevention, as well as greater clarity in defining """"""""prevention"""""""" research and establishing realistic goals, expectations, and predicted outcomes for using GEM models in chemoprevention. Accordingly, I along with Dr. Bill Nelson have assembled an outstanding team of investigators (Drs. Brown, Chodosh, Colburn, Hanahan, Hawk, Kohl, Neugut, Pandolfi, Tuveson, Van Dylce) with diverse interests and expertise from within the MMHCC and the broader community who will serve as a Scientific advisory team. Through ongoing discussions, the team will to create a dialogue among leaders from relevant disciplines with the ultimate goal of establishing a common language and clearly elucidating research objective and outcomes. In the course of such discussion, we will define specific applications for GEM models in prevention research, taking into consideration their potential benefits as well as a realistic understanding of their limitations. Co-chaired by Bill Nelson and myself, the Advisory team will: (i) establish a common language to apply prevention research to GEM models, (ii) define state-of-the-art strategies for cancer prevention and early intervention that can be informed by GEM models;(iii) explicate potential applications of GEM mice for prevention and intervention;and (iv) validate the use GEM models for cancer prevention in well-defined demonstration trials. Finally, I believe that I have demonstrated the necessary leadership skills to coalesce multi-disciplinary teams of investigators to effectively address these complex issues and I am confident that the plan I have outlined will have a high impact on our ability to effectively engage mouse models research for chemoprevention. GEM models provide a valuable but largely untapped resource for informing on cancer prevention;however their efficacy is entirely dependent on the appropriate design of experimental paradigms, the choice of relevant GEM models to address specific experimental questions, and the effective validation of studies in GEM models to human cancer. I understand these problems and I am committed to resolving them to ensure the effective use of mouse models for chemoprevention.
|Dutta, Aditya; Panja, Sukanya; Virk, Renu K et al. (2017) Co-clinical Analysis of a Genetically Engineered Mouse Model and Human Prostate Cancer Reveals Significance of NKX3.1 Expression for Response to 5?-reductase Inhibition. Eur Urol 72:499-506|
|Le Magnen, Clémentine; Dutta, Aditya; Abate-Shen, Cory (2016) Optimizing mouse models for precision cancer prevention. Nat Rev Cancer 16:187-96|
|Kobayashi, Takashi; Owczarek, Tomasz B; McKiernan, James M et al. (2015) Modelling bladder cancer in mice: opportunities and challenges. Nat Rev Cancer 15:42-54|
|Aytes, Alvaro; Mitrofanova, Antonina; Lefebvre, Celine et al. (2014) Cross-species regulatory network analysis identifies a synergistic interaction between FOXM1 and CENPF that drives prostate cancer malignancy. Cancer Cell 25:638-651|
|Wang, Jingqiang; Abate-Shen, Cory (2014) Analyses of tumor-suppressor genes in germline mouse models of cancer. Cold Spring Harb Protoc 2014:807-12|
|Abate-Shen, Cory; Pandolfi, Pier Paolo (2013) Effective utilization and appropriate selection of genetically engineered mouse models for translational integration of mouse and human trials. Cold Spring Harb Protoc 2013:|
|Irshad, Shazia; Abate-Shen, Cory (2013) Modeling prostate cancer in mice: something old, something new, something premalignant, something metastatic. Cancer Metastasis Rev 32:109-22|