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Blood test developed by KU researchers can detect early-stage lung cancer

Biosensor technology can detect lung cancer in blood when it is still curable and could be used to screen large populations at risk for the disease.

a tray of vials of blood, with three pulled out that have labels. On one label is the words "liquid biopsy test"
Lung cancer is the cause of nearly one-fifth of cancer mortalities, according to the World Health Organization. A blood test to catch it early could have a significant impact.

Lung cancer claims more lives than any other kind of malignancy, accounting for nearly 20% of all cancer deaths. Each year, more Americans die of lung cancer than of colon, breast and prostate cancers combined. Most people who develop lung cancer have a history of smoking, but 10% to 20% of people who develop lung cancer have never smoked, according to the National Cancer Institute.

When caught early, lung cancer often can be treated successfully. But the disease doesn’t cause many symptoms until after it has metastasized to other parts of the body, and by the time it’s diagnosed, it’s most often uncurable.

“Lung cancer is one of these diseases where it makes a big difference when you detect it,” said Stefan Bossman, Ph.D., professor and chair of the Department of Cancer Biology at the University of Kansas Medical Center. “Chances of survival are so much higher when you find it at the beginning.”

The National Lung Screening Trial, which was sponsored by the National Cancer Institute, concluded in 2011 that chest CT (computed tomography) scans to detect lung cancer could reduce deaths from the disease by 20%. As a result, the United States Preventive Services Task Force established guidelines recommending annual CT scans for people deemed to be at risk for lung cancer on the basis of their age and history of smoking cigarettes.

But a decade later, only about 6% of this at-risk population gets an annual CT scan. One hurdle is that not all physicians are aware that screening is covered by Medicare. And some smokers might resist screening because of fear of the disease and fear of being blamed for their nicotine addiction. CT scans also are expensive for those without insurance, and they lead to other tests, such as a biopsies, that incur their own costs and risks to the patient. Moreover, there likely are not enough CT scanners in the country to implement a population-wide program for screening adults routinely for the disease, Bossman noted.

Bossman and his colleague, Obdulia Covarrubias-Zambrano, Ph.D., research assistant professor of cancer biology, have developed a new method for detecting lung cancer early: a blood test, also known in the cancer research community as a “liquid biopsy,” that detects protease enzyme activity indicating the presence of lung cancer. Their biosensor technology is cheaper (for both patients and health systems) than a CT scan, and it detects the cancer 90% of the time, for both small and non-small cell lung cancer, even in patients with early stage 1 disease. The researchers published a description of the technology in Communications Medicine.

Their biosensor technology detects activity from different protease enzymes in blood serum. These protein-digesting proteases modify lung tissue and make space for a tumor to grow. They then get washed away, and they can be found in blood serum. Bossman and Covarrubias-Zambrano’s technology is a panel of 18 nano-scale sensors that release a fluorescent signal when these enzymes are present in a blood sample. The signal acts like a fingerprint of activity that can identify people with lung cancer. This inexpensive test produces results in just a couple of hours.

Bossman and Covarrubias-Zambrano are also working on similar biosensor-based blood tests for other cancers where it makes the most impact to catch it early, including ovarian, pancreatic and breast cancer.

“These are cancers where it’s really a must to find it at stage 1 or the transition from non- cancerous to cancerous — my favorite detection stage,” said Bossman. “In many cancers, there are tons of formative changes of the tumor tissue before it becomes cancerous. And with protease detection, if you choose the right proteases, you can detect it.”

Because the test is cost-effective and can be administered in a primary care doctor’s office, it has the potential to be widely implemented.

“We could cast a wider net, where we don't screen only at-risk patients, but can have patients screened during their yearly checkups,” said Bossman. “(These tests) are fairly good for all kinds of solid tumors.”

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