Circular RNAs: Novel Biomarkers Detectable in Blood Plasma to Facilitate Malignant Pleural Mesothelioma Diagnosis
Abstract
The proposed study will address the Fiscal Year 2021 (FY21) Peer Reviewed Cancer Research Program (PRCRP) Topic Area Mesothelioma. This study aims to develop a novel, low cost, low impact test that has the potential to significantly improve the current detection, management, and treatment strategies for mesothelioma patients. Mesothelioma is a highly aggressive, uniformly fatal cancer caused by exposure to the carcinogen, asbestos. Mesothelioma is associated with a poor patient survival (9-12 months following diagnosis) and has limited treatment options. Mesothelioma is difficult to diagnose due to a lack of effective diagnostic tests and the requirement for an invasive surgical procedure performed by a highly skilled health practitioner to obtain a sample for a definitive diagnosis. It is not always possible to perform such a high-risk procedure on elderly patients or patients with deteriorating health, which often represents the majority of mesothelioma patients. Given that mesothelioma can take 20 to 40 years to develop following asbestos exposure, most patients are diagnosed when the disease is at an advanced stage; at which point available treatments are largely ineffective. The identification and development of an improved, minimally invasive test for an accurate and early detection of mesothelioma is urgently needed. Circular RNA, a novel class of molecule that exists in both human tissue and blood, represents a promising biomarker for potential use in the detection and disease status monitoring of mesothelioma. We have recently identified up to 290 different circular RNA’s that are in higher abundance in mesothelioma cells in comparison to normal (healthy) mesothelial cells (the cells from which mesothelioma develops). This is consistent with an over-abundance of circular RNAs found in human tissue and blood components associated with cancer development/progression for other cancer types. The objective of this study is to develop a test that allows early and accurate detection of mesothelioma without the need for a surgical sample. Additionally, we will assess how effective this blood-based test is for monitoring changes in disease progression in mesothelioma patients. We will demonstrate the ability of our novel test to detect mesothelioma-specific circular RNA biomarkers by comparing a large group of mesothelioma patient-derived tissue and blood samples to matched samples from healthy and non-mesothelioma cancer patients. Additionally, we will demonstrate how this test would be used in practice to detect asbestos-induced mesothelioma through all stages of disease development using a well characterized mesothelioma mouse model. Together, this study will demonstrate how this novel, low cost, low impact test has the potential to significantly impact current mesothelioma detection and management, and demonstrate how it can be easily integrated into current screening and treatment strategies for mesothelioma patients. The FY21 PRCRP Overarching Challenges to be addressed include (1) Develop strategies and biomarkers to predict cancer risk, treatment resistance, recurrence, and advanced disease to mitigate risk in target populations; (2) Transform cancer treatment through the identification of novel biomarkers and new targets, especially for advanced disease (metastatic and/or recurrence); improve immunotherapy; and eliminate the risks of therapy- associated toxicity and; (3) Develop and improve minimally invasive methods to detect cancer initiation, recurrence, and progression. It is anticipated that the results obtained from our study will provide the foundation for future clinical studies that will further assess these circular RNA biomarker candidates in extensive cohorts of mesothelioma patients and individuals with a known history of asbestos exposure. We expect that a successful outcome of subsequent clinical trials would facilitate the implementation of a circular RNA-based diagnos
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2211052
Entities
People
- Yuen Yee Cheng
Organizations
- United States Army
- University of Technology Sydney