Development of a Blood-Based Biomarker Panel for Indeterminate Lung Nodules
Abstract
Objective and Rationale: Lung cancer screening with low-dose CT (LDCT) has been shown to reduce mortality by 20%, although there are concerns including high false positivity, cost, and radiation exposure. Of note, the false positive rate of lung cancer screening with LDCT alone was 96.4% in the National Lung Cancer Screening Trial. Although false positives may be reduced with stricter nodule criteria, blood-based markers are a promising and attractive approach to complement LDCT because of the potential to identify those subjects that may be at increased risk of developing lung cancer, that may be harboring early and potentially curable lung cancer, or that need to undergo further work-up for their indeterminate nodules. We have identified, through a series of discovery and initial validation studies, a set of protein and autoantibody biomarkers with potential for early detection. In addition to these biomarkers, we will integrate circulating microRNAs, which have recently emerged as additional promising biomarkers for lung cancer. An innovative aspect of the proposed study is integration of biomarkers from three promising platforms, protein, autoantibody, and microRNA, using the same sample set directly relevant to the intended clinical application. The diagnostic model based on selected biomarker candidates will be validated in plasma samples collected from 50 subjects with malignant lung nodules and 150 subjects with benign lung nodules from an independent screening cohort. The goal is to develop a blood-based biomarker panel and test it in a screening setting to reduce unnecessary and invasive work-up by determining among screened subjects those individuals with lung nodules who would need or would not need further diagnostic work-up and consequently to reduce mortality associated with lung cancer through more effective screening strategies. Therefore, my proposal is very much aligned with two Fiscal Year 2014 Lung Cancer Research Program Areas of Emphasis: "identify or develop noninvasive or minimally invasive tools to improve the detection of the initial stages of lung cancer," and "identify, develop, and/or build upon already existing tools for screening or early detection of lung cancer." Career Goals: I have devoted most of my efforts for the past several years applying innovative technologies for the development of lung cancer biomarkers using multiple sources of samples including prospective cohorts. My immediate career goal is to expand on important skills for a principal investigator, which for me include establishing independent research projects, supervising lab staffs, and developing and contributing to a network of investigators with domain expertise relevant to my research. My long-term career goal is to establish myself as a principal investigator in lung cancer research and expand my research activities in the field of lung cancer biomarkers using integrated approaches. This grant will provide me an excellent opportunity to expand my research beyond proteomic approaches by integrating multiple molecular profiling platforms and relating findings to tumor and subject characteristics. In the near term, this grant will provide me an excellent opportunity to get more directly involved in the design of clinical trials and in collaboration with other lung cancer investigators, particularly clinical investigators involved in the development and testing of novel diagnostic approaches to lung cancer. In the long term, this grant will be particularly useful in establishing myself as a physician scientist with expertise in translational lung cancer research and as a leader coordinating research in this field with multidisciplinary and multi-institutional investigators engaged in team science. Applicability: The biomarker panel to be developed will provide a simple, non-invasive, and cost-effective diagnostic method for early lung cancer detection with strong clinical impact due to the develop
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510127
Entities
People
- Ayumu Taguchi
Organizations
- United States Army
- University of Texas at Austin