Lung cancer, a new urine-based test is being studied

The lung cancer it is the deadliest in the world. The whole point of this high mortality rate is that it comes often diagnosed too late. In Italy, according to estimates by Airtum (Italian Cancer Registry Association), they were registered in 2022 43,900 new diagnoses (29,300 in men and 14,600 in women). They represent 15% of all cancer diagnoses in men and 6% in women.

Screening more patients could help but i Control rates remain critically low. In the United States, only about 6 percent of eligible people are screened, according to the American Lung Association. A very low percentage and compared to screening rates for breast, cervical and colorectal cancer, which all exceed 70%. However, what if the ability to detect lung cancer was as simple as doing it an inhalation of a nebulized substance and then taking a urine test?

A group of researchers at the Massachusetts Institute of Technology in Cambridge, Massachusetts, has developed gods nanosensors which target lung cancer proteins and can be administered via inhaler or nebulizer. The new method is explained this month in a study published in Science Advances. If the sensors detect these proteins, they produce a signal in the urine that can be detected with a paper test strip. It would be a revolution. “It's a more complex version of a pregnancy test but it's very simple to use,” she explained Qian Zhongan MIT researcher and co-lead author of the study.

Currently the only recommended screening test for lung cancer is the low radiation dose computed tomography. It is the best tool for the diagnosis of lung cancer in the initial stage: it is effective in discovering small lesions, as the definition of the test says, it exposes it to a very low dose of radiation, it is rapid and does not require contrast. «Our goal is to supply an alternative for early diagnosis of lung cancer that does not depend on highly equipped infrastructures” for this type of testing, he explained Edward Tan, former MIT and currently working at Prime Medicine, co-author of the survey. “Most developing countries do not have such resources” and, to be honest, neither do large regions of richer countries.

The sensors consist of polymeric nanoparticles coated with DNA barcodes, short DNA sequences that are unique and easy to identify. The researchers designed the particles to be affected by protease enzymes linked to stage I lung adenocarcinoma. Upon contact, proteases detach these elementary DNA sequences which enter the bloodstream and are then expelled in the urine. A test strip can detect its presence, thus providing results about 20 minutes from the time it is immersed. The revolutionary aspect is that these nanosensors that target lung cancer proteins by triggering this reaction (which will then be useful in the examination) can be nebulized and administered precisely with an inhaler or a nebulizer. How to make an aerosol.

The invention was tested on genetically modified mice to develop lung cancers similar to those that affect humans. Using aerosol nebulizers, the team administered 20 sensors to mice with equivalent stage I or II cancer. Afterwards, taking advantage of a machine learning algorithm, they identified the four most accurate sensors. With a specificity of 100%, these four sensors showed a sensitivity of 84.6%. “One advantage of using inhalation is that it is non-invasive, and another is that it is distributed throughout the lung quite evenly,” Tan explained. The time from inhalation to detection is also relatively quick: In mice, the entire process took a couple of hours, and Zhong speculated that it wouldn't take much longer in humans.

The technology has also been tested some time ago in a phase one trial but in one injectable version and intended to diagnose liver cancer and non-alcoholic steatohepatitis. This mechanism also works in tandem with the following urine test. But the system can be adapted for various clinical purposes: for example, in the MIT laboratory, work is being done to develop inhalable sensors to quickly distinguish between viral, bacterial or fungal pneumonia such as pulmonary mycosis. Remaining instead to the lungs, it could be useful for identifying asthma and chronic obstructive pulmonary disease.

Is it really a revolution? Medscape asked for an opinion from Gaetano Rocco, thoracic surgeon and researcher specializing in lung cancer at Memorial Sloan Kettering Cancer Center in Middletown, New Jersey, obviously not involved in the investigation. According to the expert the technology is certainly «innovative». However, difficulties may arise when applying it to people. In fact, many are factors involved in regulating fluid volume, potentially interfering with the ability to detect compounds in urine. Diet, hydration, medications, kidney function and some chronic diseases could in fact limit the effectiveness of the invention. Plus, it might take multiple types of sensors given the extreme variety of human tumor types. In any case, the team – well aware of these limitations – is starting to analyze human biopsy samples to see whether the same sensors that worked so well in mice could also be used in humans. If all goes well, the next experimental steps can be carried out on humans or non-human primates.