Deciphering the Role of mRNA Dynamics and Modifications for Prostate Cancer Progression
Abstract
Prostate cancer remains the second leading cause of cancer-related deaths in men of the United States. Though ~80% of patients will remain cancer free after curative surgery, the remaining 20% account for the severity of the metastatic disease. This is partially because our current diagnostic options fail to classify non-aggressive from aggressive tumors starting from the primary tumor. This leads to potentially invasive treatment options with poor therapeutic response for advanced disease. The focus of this proposal is to identify and understand the biological mechanisms that lead to aggressive prostate development, therapy resistance, and progression through studying oncogenic adaptation pathways that reconstitute gene expression. One fundamental hallmark of cancer cells is their adaptation to cellular stress allowing for cell survival. By studying the cancer stress response, we can gain access to a tremendous window of opportunity for understanding this particular vulnerability of cancer cells, allowing us to create novel therapeutic strategies. Strikingly, our research suggests that there is a unique regulation of a subset of proteins that are required for this cancer cell adaption to stress. These novel targets are selectively expressed by an adaptive stress response rewiring our genetic code through mRNA translation during advanced cancer development. The mechanism of action for the regulation and basic biology of these epi-transcriptomic mechanisms are poorly understand in disease. This proposal will utilize several state-of-the-art technologies including deep sequencing and bioinformatic analysis to study this adaptation and the factors involved in the cancer stress response required for tumor progression. Thereby, our research will unravel the genetic and molecular mechanisms that underlie and maintain aggressive cancer cell survival under stress and contribute to the identification of novel targets that detect clinically relevant disease during early stages of prostate cancer. Furthermore, this research will provide the rationale for designing innovative pharmacological approaches to target the earliest events of tumorigenesis, with the long-term objective of eliminating metastatic prostate cancer and enhancing the well-being and health span of individuals suffering from this disease.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310122
Entities
People
- Crystal S Conn
Organizations
- United States Army
- University of Pennsylvania