Deciphering the Complete Oncogenic Proteome and Its Role for Prostate Cancer Progression
Abstract
After curative surgery and therapy, the majority of prostate cancer patients will remain cancer-free, and yet prostate cancer remains the second leading cause of cancer-related deaths in men in the United States. This is partly due to the severity of the metastatic disease and the acquired resistance to drug therapies as the cancer progresses. Currently, our diagnostic options fail to classify non-aggressive from aggressive tumors starting from the primary tumors removed at surgery. This can lead to potentially missed treatment options after early detection, with poor therapeutic response for advanced disease. Despite these limitations, there arise cellular adaptations that oncogenic cells rely on for their survival and tumor progression that may offer new avenues for diagnosis and future therapies. We discovered an adaptive pathway that is required for tumor survival, enhanced by current clinical therapies for promoting resistance, and linked to metastasis in patient samples. The biological activation of this stress adaptation, the factors at play, and the downstream alterations on the cancer epigenome augmented remain unknown. The focus of this proposal is to understand the biological mechanisms of cell adaptations that occur early in primary tumors to promote aggressive prostate development and therapy resistance. Our aim is to understand and map these stress response pathways, which are known to reconstitute gene expression through regulating mRNA translation. We will utilize several state-of-the-art technologies including deep sequencing and mass spectrometry coupled to bioinformatics to study this adaptation and the factors involved in the prostate cancer stress responses required for tumor progression. Collectively, we seek to map the adaptive post-transcriptional aspects of gene expression, identify full protein sequences missing from our current annotated genomes, and determine the factors and oncogenic signaling that command this adaptive response utilized by aggressive prostate cancer. Our results will gain access to a tremendous window of opportunity for understanding prostate cancer progression and this targetable vulnerability of aggressive tumors. By discovering the mechanism of regulation for these processes, we have the potential to identify novel functional biomarkers for diagnostics in primary tumors that can improve our current therapeutic strategies, while revealing innovative targets.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310082
Entities
People
- Crystal S Conn
Organizations
- United States Army
- University of Pennsylvania