Two-Step Approach for Advanced Prostate Cancer Management: Targeting PLK1 After Castration
Abstract
One of the major clinical challenges in prostate cancer is the fact that tumor cells become resistant to current therapies, either to androgen deprivation therapy or to existing drugs. Most prostate tumors are initially responsive to androgen ablation therapy; however, relapse is common and this leads to castration (which mimics androgen deprivation therapy)-resistant prostate cancer with an increased propensity to metastasize. These castration-resistant cells are believed to be prostate cancer stem cells (CSC). In fact, it is reported that prostate cancer stem cell population can be enriched after androgen deprivation both in cell culture systems and prostate cancer patients. CSCs are distinct populations of tumor cells that have unique features that make them resistant to the current therapies. Thus, it is logical to speculate that prostate tumor progression or recurrence can be inhibited by targeting molecules that CSC depends on, such that their expression levels are increased after castration. One such target is polo-like kinase (PLK1). The objective of this proposal is to determine whether PLK1 is a potential molecular target in the treatment of men who develop therapy-resistant prostate cancer. This proposal will determine the potential for a new two-step approach that targets PLK1 after castration using relevant murine model systems. As such, this proposal is expected to provide the foundation for novel combination therapeutic strategies. This study can be used to identify patients who might benefit from PLK1 targeting in combination with other therapy, such as castration (surgical or chemical). The ultimate goal of this study is to use patient samples to test potential efficacy of molecular intervention such as PLK1 inhibition in combined therapy with other known approaches and then apply the data we generated into patient care. As such, a successful outcome will lay the foundation for better treatment options for prostate cancer patients. The studies are fully consistent with the goals of the Department of Defense s funding mechanism and are expected to provide better treatment options for cancer patients in general.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510105
Entities
People
- Meejeon Roh
Organizations
- Northwestern University
- United States Army