Prostate Cancer Recurrence: models and mechanisms

Project: Research project

Project Details


A major clinical problem in prostate cancer is that of tumor recurrence following initial apparently
successful therapy. It is widely believed that recurrent tumors may arise from a small number of “cancer
stem-like cells” that survive the initial therapeutic intervention and which have the capacity to regenerate the
tumor. However, this idea has been difficult to test in vivo without manipulation of the cancer cells outside
their native environment in the animal. Here we propose a lineage-tracing strategy to examine the
competence of specific prostate epithelial cell types (“castration-resistant Nkx3.1-expressing cells or CARNs”
and Bmi1+ cells) to regenerate tumors following androgen ablation in mice (Aim 1). We will further examine
whether recurrent tumors driven by specific oncogenic mutations preferentially arise from particular cell
populations of stem-like cells within a regressed tumor and the role of the androgen receptor (Aim 2). Finally,
we will employ lineage ablation of specific cell types within a regressed tumor to assess the relative
contributions of specific stem-like cells (CARNs and Bmi1+ cells) to prostate cancer relapse (Aim 3). In these
studies will use novel approaches to define the significance of specific prostate cell types in tumor relapse
following androgen ablation. This proposal if successful will have a major impact on our understanding of the
cellular origins of recurrent prostate cancer and will facilitate efforts aimed at successfully eradicating the
Effective start/end date6/1/145/31/18


  • National Cancer Institute (5R01CA167966-04)


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