Early Lung Cancer Detection Using Plasmonic Nano-Aperture Label-Free Imaging of Cancer Exosomes
Abstract
Although lung cancers still carry high mortality, early detection of lung cancer at the earliest stages allows for curative management of the disease. Patients who have are at risk of developing lung cancers, particularly those with more than 20-pack-per-year history of smoking, are currently being screened for lung cancer using yearly low dose computed tomography (CT) scans. However, a CT scan is highly sensitive but often not specific enough to render a definitive diagnosis. Not knowing ahead of time which nodules are benign or malignant obligates the need for additional procedures such as a biopsy or surgery can subject the patient to potential harms if the nodule reflects a benign process. There is a strong need for complementary testing to provide additional specificity of the LDCT for lung cancer. An ideal test will be a blood test, also known as liquid biopsies, that would be sensitive enough to detect cancer specific elements even at early stages of disease. The most commonly used liquid biopsies to detect the presence of cancer is to measure levels of cancer-specific DNA released in the blood. In advanced cancers, sufficient levels of spilled DNA is found in the blood to make a liquid biopsy a very convenient way to identify cancer-specific genetic alterations that could help direct the use of specific drugs targeting the specific mutated proteins. However, early-stage cancers fill very little DNA in the blood, and therefore makes cancer detection extremely difficult. Because of the high level of false negativity, liquid biopsy looking for cancer-specific DNA is not a very sensitive test to be very informative about the nature of a lung nodule found on LDCT. Exosomes are small cell bodies or vesicles actively secreted by cells as a way to discharge excessive amounts of proteins, lipids, DNA, and RNA and as a form of communications between cells locally and at distance. Compared to normal cells, cancer cells tend to secrete high levels of exosomes due to the relatively higher levels of metabolic activity that generates much more byproducts of cellular activity. We have developed a small device called integrated biochip imaging technology (iBIT) that allows direct measurement of exosomes from a small drop of blood. The contents of the exosomes could be evaluated further using specialized probes to measure the contents of the exosomes at the same time. Because this is a specialized microscope that could count the labeled exosomes directly, we could directly measure and distinguish the presence of cancer exosomes and the proportion of total exosomes in that drop of blood that belongs to cancer. We have found that iBIT is a highly sensitive test that could easily identify the presence of cancers, even stage I cancers of multiple origins, and is able to distinguish cancer patients from healthy subjects with >98% specificity. Our proposal for the Fiscal Year 2022 Lung Cancer Research Program Area of Emphasis is on identifying innovative strategies for the screening and early detection of lung cancer. We believe iBIT is a highly sensitive and specific test that could be used to complement LDCT screening by rendering the verdict on whether a nodule could be benign or malignant. While the research is still early, we believe iBIT has so far achieved impressive performance for us to take it to the next level to evaluate clinical samples from lung cancer screened patients. These precious samples come from a Department of Defense-funded study that was developed several years ago to collect biospecimen from military personnel at the Veterans Administration hospitals across the United States that were being screened for lung cancer. For this two-year project we will provide the evidence that iBIT could be developed for lung cancer screening purposes. This will benefit all patients who are currently being screened using LDCT and therefore will have a great impact on military personnel and their family member
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310639
Entities
People
- Steven Lin
Organizations
- The University of Texas MD Anderson Cancer Center
- United States Army