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Project

Epigenetic regulation of bladder cancer progression

Funder: Bladder Cancer Advocacy Network

Funding period
USD 300 K
Funding amount
Abstract
The Cancer Genome Atlas (TCGA) has recently reported a comprehensive analysis of MIBC, which identified the prevalence of alterations of epigenetic regulatory genes in nearly all MIBC examined thus far. Thus, our proposed studies are based on the hypothesis that MIBC is driven in part by alterations of the epigenetic program and that modulation of this program may provide new approaches for therapeutic intervention. Our plan is to evaluate the functional roles of epigenetic regulatory genes that are frequently altered in MIBC, namely KDM6A, MLL2, CREBBP, EP300, and ARID1A. These studies will provide an essential foundation to understand the significance of altered epigenetic regulation for MIBC, and will establish preclinical models to evaluate the consequences of targeting the epigenome for treatment of MIBC. The near-term benefit of our studies for improved patient care will be the establishment of clinical trials that target the epigenome based on findings from our preclinical studies. To accomplish our goals, we have assembled an outstanding team of investigators from Columbia University Medical Center and Memorial Sloan Kettering Cancer Center with complementary expertise in cancer biology, pathology, urology and medical oncology. Working together, we have established innovative methodologies to develop orthotopic tumor models as well as novel three-dimensional culture of “organoids” of bladder cancer. These models will enable functional analyses of epigenetic regulators in MIBC and will be used to perform preclinical investigations that presage subsequent clinical interventions. Notably, our novel approach will establish new paradigms to enable investigations of other gene/pathways that are of potential significance for treatment of bladder cancer, and therefore will have broad implications for the field.
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System

Categories
  • FOR (ANZSRC)

    1112 Oncology and Carcinogenesis

  • RCDC

    Biotechnology

  • RCDC

    Human Genome

  • RCDC

    Cancer

  • RCDC

    Genetics

  • RCDC

    Urologic Diseases

  • HRCS HC

    Cancer

  • HRCS RAC

    2.1 Biological and endogenous factors

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Basic Science