Investigating Long Noncoding RNAs as Predictive Biomarkers in Prostate Cancer
Abstract
Prostate cancer is a heterogeneous disease and is still the second most common cause of cancer-related deaths in men in the United States. While many prostate cancers are indolent, an important subset of patients experience disease recurrence after conventional therapy and progress to castration-resistant prostate cancer (CRPC), which is currently incurable. For these men, optimal treatment is not known. There are many biomarkers and gene signatures that can predict overall prognosis, but do not specifically predict response to a particular therapy. We need better biomarkers to predict which patients will respond to which therapeutic approaches in order to truly personalize our treatment to each unique tumor. Traditionally, protein-coding genes have served as the foundation of biomarker development. However, there is increasing evidence that non-protein coding genes (genes that make RNA but do not become proteins) can have complex biological functions of their own. Long non-coding RNAs (lncRNAs) in particular are emerging as an important class of molecules that drive the development and progression of prostate cancer. LncRNAs are RNA species that share many similarities with protein coding genes, despite the fact that they are non-coding (not translated into proteins). While a large number of lncRNAs exhibit tissue- and cancer-specific expression, their utility as diagnostic and prognostic biomarkers is just starting to be explored. LncRNAs are involved in pathways important in treatment response in prostate cancer. It is clear that lncRNAs are an underexplored area of cancer biology and are involved in a range of cellular processes important to cancer treatment. We hypothesize that by comprehensively profiling all known and newly discovered lncRNAs across seven different clinical cohorts with nearly 2500 patients, we will identify new lncRNAs associated with treatment resistance. We also hypothesize that the functional characterization of top candidate lncRNAs such as AC009478.1 will provide the foundation for developing novel therapeutic strategies in the future. This project will provide a comprehensive understanding of the lncRNA landscape in prostate cancer in the largest study of its kind to date, with almost 2500 samples. These results will expand our understanding of aggressive prostate cancer, define the role of novel, prognostic lncRNAs in progression and treatment resistance, and determine the clinical utility and mechanism of action of a new lncRNA biomarker AC009478.1. We believe our multidisciplinary approach will provide a foundation for the investigation of lncRNAs in prostate cancer both now and in the future. Furthermore, completing the aims of this proposal may lead to the development of AC009478.1 as a clinically useful biomarker to identify those patients with lethal disease and help determine if certain therapies will be more effective. Our proposed research will explore the potential of lncRNAs as clinical biomarkers and therapeutic targets in prostate cancer. We believe the studies proposed in this grant will contribute high-impact work in the field of prostate cancer research and will enhance our understanding of disease biology while also providing immediately translatable tools for the clinical management of patients. Novel lncRNA biomarkers will allow physicians to select therapies based on the genetic makeup of an individual s tumor and allow for truly personalized care.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610747
Entities
People
- Felix Y. Feng
Organizations
- United States Army
- University of California, San Francisco