Characterization of FGFR Signaling in Prostate Cancer Stem Cells and Inhibition via TKI treatment
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Characterization of FGFR Signaling in Prostate Cancer Stem Cells and Inhibition via TKI treatment

  • Author(s): Ko, Juyeon
  • Advisor(s): Donoghue, Daniel
  • et al.
Abstract

Cancer stem cells have been extensively studied in numerous cancers, however, there is no clear identification of this rare subpopulation and a means for an effective therapy targeting these cells although they are implicated in tumor initiation, drug resistance, reoccurrence and metastasis. The review article in Chapter 1 emphasizes how the cancer stem cells exploit a ubiquitination modification in human cancers and metastasis. Ubiquitination is a type of post-translational modification that extends the function of proteins such as stabilizing oncogenic signals and recruiting signaling proteins that favors the cancer progression beyond our current discoveries and knowledge. The studies of cancer stem cells may help us better understand the heterogeneous disease collectively termed cancer. One type of cancer in which the cancer stem cell theory may lead to alternative therapeutic options is prostate cancer. Chapter 2 presents research hypothesizing that prostate cancer stem cells (CSCs) take advantage of Fibroblast Growth Factor Receptor (FGFR) signaling for survival and proliferation among the bulk tumor and possess the ability to survive the current therapy of androgen deprivation but can be targeted by FGFR inhibitors. As tyrosine kinase inhibitors (TKIs) have shown great effectiveness for some cancers, they have shown only modest outcome in prostate cancer treatment. The research presented here focuses on studying the FGFR signaling in the rare subpopulation shown as 3-dimensional spheroids compared to a bulk tumor represented as monolayer cells. This study reveals that FGFR signaling in the prostate CSCs promote their stemness characteristics and these CSCs may possess increased metastatic potential shown by changes in their gene expression. This study provides a novel in vitro model to study FGFR signaling in prostate cancer cell lines and utilizes a novel induced pluripotent stem cell-derived cell line to improve our understanding of prostate CSCs at a cellular and molecular level. The findings from this research may assist in screening for patient subgroups who would benefit from the TKI treatment targeting FGFR as an alternative treatment option.

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