Brushing the Airway to Detect Lung Cancer Earlier

More people die from lung cancer than from any other cancer type. In 2017 alone, the estimated number of lung cancer deaths in the United States will exceed 155,000. Tobacco smoking is the prime culprit underlying the development of most lung cancers. Sadly, most people are diagnosed with late-stage disease that has spread to other parts of the body and is difficult to treat.

Low-dose computed tomography (CT) screening can be used to detect lung cancer at earlier stages, but false-positive results, suggesting cancer is present when it is not, are common. False-positive results mean that many people who have benign lung nodules must undergo invasive and painful follow-up tests to see if they have cancer. Having experienced the limitations of low-dose CT screening firsthand in his pulmonary practice, Avrum Spira, a physician, researcher, and entrepreneur at Boston University, was determined to change that. With NCI funding, he is transforming the paradigm of early lung cancer detection and screening.

Avrum’s approach makes use of the fact that tobacco smoke wreaks havoc on the cells that line the upper airway and the lungs, causing damage to their DNA that can eventually lead to cancer. Drawing on previous ideas about how the toxins in cigarette smoke damage a much larger “field” of tissue than the precise spot where a malignant tumor will eventually grow, he reasoned that it might be possible to test samples of upper airway tissue for signs of genomic damage that are associated with lung cancer deep within the lung.

To determine whether cells in the upper airway, which are much easier to sample than cells in a lung nodule or tumor, can provide a sign that a person has cancer, he piggybacked on a minimally invasive endoscopic procedure called bronchoscopy. This procedure is often used as an initial diagnostic test for smokers and former smokers who have lesions in their lungs that are suspicious for cancer. As a stand-alone test, however, bronchoscopy misses 40%–50% of lung cancers because many nodules and tumors are beyond the reach of a bronchoscope.

To collect cells from the upper airway for analysis, Avrum and his team used a bronchoscope equipped with a brush. The collected cells were then analyzed for molecular changes associated with lung cancer. With this approach, they identified a characteristic set of genomic changes in cells from the upper airways of patients with lung cancer.

In 2007, Avrum started a company that conducted two clinical trials of this “bronchial genomic classifier” in patients who had not been diagnosed with lung cancer from 28 medical centers—26 in the United States, one in Canada, and one in Europe. The trials, which were supported by funding from NCI's Small Business Innovation Research (SBIR) Program and venture capital, were completed in 2014 and validated that this test could determine the likelihood that lung nodules were either benign or malignant.

The company was acquired the following year by Veracyte, a publicly traded genomic diagnostics company, which launched the test commercially as Percepta^®. In 2017, Medicare began covering Percepta^® as a diagnostic tool to expand the use of bronchoscopy in detecting lung cancer.

“It’s gratifying to see something that started at the bench make it all the way to a patient,” Avrum reflected, “but it was a long journey—more than 10 years.” Acknowledging NCI’s involvement both in the basic research and commercialization, he said, “Percepta^® is now a product because of NCI’s support.” Striving to develop even better technology, he has found, with funding from NCI’s Early Detection Research Network, that some of the same molecular damage seen in the upper airway is also present in the nose, which would enable even easier and less-invasive testing.