Abstract

There is no cure for advanced prostate cancer (PCa), and taxane chemotherapy is the only treatment option once other therapies have failed. However, this is problematic since all patients eventually develop chemoresistance. Emerging treatments for advanced PCa have shown promise at the benchside, but clinical trials have not resulted in newly approved drugs due in part to redundant survival pathways utilized by prostate tumor cells to maintain therapy-resistance. Using RNAsequencing—an innovative approach for quantifying gene expression changes—this dissertation sought to elucidate chemoresistance-associated molecular pathways as a catalyst to develop new therapeutic targets. Results revealed a differential upregulation of stemness-associated genes in PCa cells selected for chemoresistance. In addition, chemoresistant cells formed robust stem cell prostaspheres compared to chemosensitive cells, and expressed other markers of cancer stem cells. Overall, these findings support the hypothesis that PCa chemoresistance is driven by cancer stem cells.

LLU Discipline

Microbiology and Molecular Genetics

Department

Basic Sciences

School

School of Medicine

First Advisor

Casiano, Carlos A.

Second Advisor

Brantley, Eileen

Third Advisor

Payne, Kimberly J.

Fourth Advisor

Unternaehrer, Julia

Fifth Advisor

Wang, Charles

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

2018

Date (Title Page)

8-2018

Language

English

Library of Congress/MESH Subject Headings

Prostatic Neoplasms; Prostate Cancer -- Treatment; Stem Cells

Subject - Local

Chemoresistance; RNA Sequencing; Gene Expression;

Type

Dissertation

Page Count

168

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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