Targeting Pim Kinase/lncH19 Axis in Enzalutamide-Resistant Prostate Cancer
Abstract
The goal of this project is to understand the mechanisms of therapeutic interventions in prostate cancer (PCa) and to identify approaches to overcoming such resistance. This project will identify treatment targets for castration-resistant PCa. Interim outcomes include an understanding of how changes in stem cell genes impact PCa development. In particular, the Principal Investigator (PI) will pursue studies further examining features of her preliminary data on stem cell factors in drug resistance – particularly the impact of a novel signaling cascade, SOX2 (a reprogramming transcription factor in the resistant cells) and H19 (a long noncoding RNA), both of which are influenced by expression of a factor, Pim-1, that is overexpressed in PCa. The PI, Dr. Neha Singh, is mentored by a well-established translational scientist in the signal transduction field, Dr. Andrew Kraft. The Researcher Development Plan details the PI’s development of expertise and tools of biochemistry, molecular biology, and proteomics that will address the question of how drug resistance develops in PCa. The PI has developed novel prostate organoid systems from genetically engineered mouse models to better understand this mechanism. This project will lead to development of novel therapeutic combinations of Pim Kinase inhibitor and Enza to treat PCa.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810533
Entities
People
- Neha Singh
Organizations
- United States Army
- University of Arizona