Studies have shown that a simple urine test can reveal the existence of lung cancer in mice.
High risk groups of lung cancer (such as “old smokers”) usually need to be screened by computed tomography (CT) to detect lung tumors. However, this test has a very high false positive rate because it can also detect benign nodules in the lungs.
According to the report of mcmus consulting, MIT researchers have developed a new method for early diagnosis of lung cancer: a urine test, which can detect the presence of proteins related to the disease. This non-invasive test can reduce the number of false positives and help detect more tumors early in the disease.
MIT engineers have developed nanoparticles that can be delivered to the lungs, in which tumor related proteases cut peptides on the surface of the particles and release reporter molecules, which can be found by urine tests
Early detection is very important for lung cancer, because patients who can be found before the tumor spreads to a distant position in the body will have a five-year survival rate of at least six times higher.
Sangeeta Bhatia, Professor John and Dorothy Wilson, Department of Health Science and technology, electronic engineering and computer science, Massachusetts Institute of technology, said, “if you pay attention to cancer diagnosis and treatment, you will re recognize the importance of early cancer detection and prevention. We urgently need new technologies that can detect cancer early and intervene.” She is also a member of Koch Institute for integrated cancer research and the Institute of medical engineering and science.
Bhatia and her colleagues found that the new test, based on nanoparticles that can be injected or inhaled, can detect tumors as small as 2.8 cubic millimeters in mice.
Bhatia is the corresponding author of the study. The research results are published in the journal Science Translational Medicine. The first authors of the paper are Jesse Kirkpatrick and AVA soleimany, graduate students from MIT and Harvard respectively, and Andrew Warren, a former MIT graduate student, who is now a partner of third rock ventures.
Targeted lung tumor
For several years, Bhatia’s laboratory has been developing nanoparticles that can detect cancer through protease interaction. These enzymes help tumor cells escape their original location by cutting off proteins in the extracellular matrix.
To find these proteins, Bhatia created nanoparticles coated with cancer-related protease targeting peptides (short protein fragments). The particles accumulate at the tumor site, where the peptide is cleaved, releasing biomarkers, and then detected in urine samples.
Previously, Bhatia’s laboratory has developed sensors for colon and ovarian cancer. In their new research, researchers hope to apply the technology to lung cancer, which causes about 150000 deaths in the United States every year. People who receive CT scans with positive results usually undergo biopsies or other invasive tests to find lung tumors. Bhatia said that in some cases, this process may lead to complications. Therefore, noninvasive follow-up test will help to determine which patients really need biopsy.
“CT scan is certainly a good medical tool and can see a lot of things. The problem is that 95% of the cancer it finds is not cancer. Therefore, a large number of positive patients must be biopsied,” she said
In order to customize the sensor for lung cancer, the researchers analyzed a cancer related gene database called Cancer Genome Atlas and identified the proteases rich in lung cancer. They created a set of nanoparticles wrapped in 14 peptides that could interact with these enzymes.
The researchers then tested the sensors on mice with two different cancer models. Both cancer models were treated with gene mutations, resulting in the natural development of lung cancer. To prevent background noise from other organs or blood, the researchers injected these nanoparticles directly into the airway.
Using these sensors, the researchers conducted diagnostic tests at three time points: 5 weeks, 7.5 weeks and 10.5 weeks after the tumor began to grow. In order to make the diagnosis more accurate, they used machine learning to train algorithms to distinguish the data of tumor mice and healthy mice.
Using this method, the researchers found that they could accurately detect tumors in one of the mouse models as early as 7.5 weeks, with an average of only 2.8 cubic millimeters. In another mouse model, tumors can be detected at 5 weeks. The success rate of the sensor is also equal to or even better than that of the CT scan performed at the same time point.
Reduce false positives
The researchers also found another important function of the sensor, which can distinguish early lung cancer from non cancerous pneumonia. The common pneumonia in smokers is one of the reasons for a large number of false positive CT scans.
Bhatia envisages the use of nanoparticle sensors as a non-invasive diagnostic method for people with positive screening test results, so that it is possible not to need biopsy. Her team is studying particles that can be inhaled as dry powder or through an atomizer for human use. Another potential application is to use these sensors to monitor the response of lung tumors to treatment, such as drugs or immunotherapy.
Bhatia added, “the next step is to use this technology in patients who have cancer and are being treated to monitor whether they are using the right drugs.”
She is also studying a sensor that can be used to distinguish viral and bacterial pneumonia, help doctors determine which patients need antibiotics, and even provide supplementary information for nucleic acid tests (such as the nucleic acid test developed for covid-19). Glympse bio, co founded by Bhatia, is also working to develop this method to replace relying on biopsy to evaluate liver diseases.
The research was supported by Koch Institute (core support) awarded by National Cancer Institute, National Institute of Environmental Health Sciences, National Science Foundation Supported by the Ludwig Center for molecular oncology of MIT, the marble Center for cancer nanomedicine of Koch Institute, the frontier research program of Koch Institute for advanced lung cancer and Johnson and Johnson.
Responsible editor: CT