Circulating Exosomes as Biomarkers for Lung Cancer Early Detection
Description: Lung cancer is the leading cause of cancer death among men, and the second leading cause among women worldwide. Lung cancer screening with low-dose computed tomography (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%. Blood-based biomarkers 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, or 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 blood-based biomarker candidates from multiple platforms (protein, autoantibody, lipid, glycan, and microRNA) for which we obtained independent evidence for their potential utility to discriminate asymptomatic lung cancer subjects from matched controls. In addition to these biomarkers, we will integrate circulating exosomes, which have recently emerged as additional promising biomarkers for lung cancer. The focus of this proposal is on (1) to identify potential exosome biomarkers using pre-diagnostic plasma samples collected from subjects that were later diagnosed with lung cancer; (2) to assess and compare the performance of exosome biomarkers with that of other validated biomarkers side by side in an independent pre-diagnostic plasma sample set to develop an optimal biomarker panel; (3) to validate the assembled biomarker panel in plasma samples collected in a lung cancer screening setting. An innovative aspect of the proposed study is integration of biomarkers from multiple promising platforms, using the same sample set directly relevant to the intended clinical application.
The proposed biomarker panel will provide a simple, non-invasive, and cost-effective diagnostic method for early lung cancer detection with strong clinical impact due to the development of novel diagnostic procedures for lung cancer. Therefore it will contribute improvement of efficiency of LDCT screening in population with high risk of lung cancer. As the biomarker panel will be tested in the context of our intended clinical application, the panel will be translated immediately into a powerful diagnostic tool for the management of high-risk participants. Thus, if successful, this non-invasive blood-based biomarker panel will allow us to achieve a better screening accuracy, to diagnose lung cancer earlier, and to provide less invasive and cost effective therapeutic options, and consequently will reduce mortality associated with lung cancer through more effective screening strategies.
Funder: American Cancer Society
Amount: $792,000
Funding type: award
Start date: 2018-03-01
End date: 2018-08-31
Investigator: Ayumu Taguchi
Institution: The University of Texas MD Anderson Cancer Center
Subfield: Molecular Biology
Domain: Life Sciences
Funded outputs count: 0
Funder award ID: 130144 - RSG-18-001-01-TBG
OpenAlex ID: G4745011301