Genomic Analyses of Prostate Cancer Reveal the Molecular Basis of Disease Heterogeneity

Chalmers, Zachary R

doi:https://doi.org/10.21985/n2-yj8m-kf30

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Genomic Analyses of Prostate Cancer Reveal the Molecular Basis of Disease Heterogeneity

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Prostate cancer is the most common cause of cancer among men in the United States, and the second most common cause of cancer-related death, accounting for significant morbidity and mortality. This dissertation describes the genomic landscape of prostate cancer from multiple angles to identify mechanisms of disease heterogeneity amongst patients. This goal is approached through six chapters of published and unpublished works reviewing the current understanding and describing our efforts to expand the current state of knowledge. Specifically, we will discuss the genomic differences of prostate cancer in men of African or European ancestry, and how those difference may account for disparities in outcomes between these two groups. Then, we will present data on the genomic drivers of early onset prostate cancer and explore novel approaches to treatment of TMPRSS2-ERG driven tumors. Finally, we will show how tissue recombination models of advanced prostate cancer with neuroendocrine differentiation can be used to generate a novel gene signature predictive of treatment response and clinical outcomes. Together, these works show the diverse genomic landscape of prostate cancer and highlight the numerous approaches required to understand this disease. Ultimately, we hope that through this and future works, we will enable a more personal patient-centered approach to care by revealing the specific determinants in a patient’s tumor that drive their disease, impact treatment response, and determine prognosis.

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