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Analysis of bladder cancer precursor formation as a basis for early therapeutic intervention

Institution: Stanford University
Investigator(s): Aaron Kershner,
Award Cycle: 2019 (Cycle 29) Grant #: T29FT0629 Award: $193,320
Subject Area: Cancer
Award Type: Postdoctoral Fellowship Awards
Abstracts

Initial Award Abstract
Smoking is the largest single cause of bladder cancer, the fourth most common cancer in men. The vast majority of bladder cancers originate in cells lining the interior of the organ, called epithelial cells. A small subpopulation of epithelial cells are stem cells that supply new cells during normal tissue regeneration and repair. The remarkable growth capacity of bladder stem cells is unleashed during malignant transformation, as rare stem cells are the source of bladder cancer. Prior to overt tumor formation, aggressive stem cell-derived cells expand to many distant regions of the tissue. One remarkable feature of this ‘pre-malignant’ growth is that these cells are often derived from a single stem cell, and are thus clones. Despite the critical importance of the clonal stem cell expansion for establishment of bladder cancer, we know little about how this expansion initiates. Understanding how bladder stem cells proliferate during the early stages of tumorigenesis may enable development of diagnostics for early detection of cancer precursors as well as treatments that may limit their spread. The proposed research uses a mouse model for bladder cancer to better understand the clonal growth of stem cells in the early stages of bladder cancer, and includes the use of drug treatments to test therapeutic approaches for halting their expansion.