Stomach cancer is one of the more challenging cancers to diagnose and treat. In particular, stomach cancer diagnosis requires an endoscopy, which necessitates prolonged fasting and preparation, instead of a simple imaging device. American researchers have discovered a method to easily identify stomach cancer using medical imaging. They have even developed a missile therapy that accurately targets stomach cancer using a similar principle.
A team of researchers led by Professor Shadi Espahani at Massachusetts General Hospital (MGH), affiliated with Harvard University, noted on the 12th in the international journal Science Translational Medicine that they have developed a method to easily diagnose and treat stomach cancer using fibrin, a protein involved in blood clotting.
Stomach cancer has a high incidence rate in South Korea. According to national cancer registration statistics, among 277,523 new cancer patients in 2021, 29,361 were stomach cancer patients, ranking fourth overall. This accounts for 10.6% of all cancer patients. The mortality rate also ranks fourth among all cancer types. While there are many stomach cancer patients, like other cancers, it can be adequately treated if detected early. However, diagnosis is relatively challenging.
Positron emission tomography (PET) has recently been widely used for cancer diagnosis, but its accuracy is lower for stomach cancer. PET identifies cancer tissue by exploiting the fact that cancer cells consume more glucose than normal cells. However, stomach cancer tissue does not exhibit increased glucose consumption, making accurate diagnosis difficult. Consequently, stomach cancer is primarily diagnosed through endoscopy, which has limitations in accessibility compared to imaging diagnostic equipment.
The MGH research team focused on fibrin while searching for new target substances to conceal stomach cancer tissue. Fibrin assists in preventing bleeding when it occurs and is more abundant in stomach cancer tissue than in other tissues. If the amount of fibrin in the tissue can be accurately evaluated, it would imply that stomach cancer can be easily detected.
The researchers created a protein that binds to fibrin and combined it with copper radioactive isotopes to develop a contrast agent for PET. This contrast agent makes the target tissue visible during imaging of internal body tissues. By measuring the radiation emitted from copper based on the amount of protein bound to fibrin, the quantity of fibrin can be assessed. This means that the location of stomach cancer tissue, which contains a high amount of fibrin, can be accurately confirmed through imaging.
The researchers recruited seven actual stomach cancer patients to confirm whether stomach cancer diagnosis using fibrin was feasible. Of the seven participants, three had undergone cancer treatment, and two were terminal patients whose cancer cells had metastasized to other organs. The patients received a contrast agent that binds to fibrin and underwent PET imaging. As a result, all 53 cancer tissues previously diagnosed in existing patients were confirmed through imaging.
Building on the early diagnosis of stomach cancer using fibrin, radioactive drugs that selectively attack only stomach cancer cells have also been developed. These radioactive drugs are a type of missile that emits radiation within specific tissues to target cancer cells. Traditional radiation therapy, which administers radiation from outside the body, has side effects of attacking both cancer and normal cells. Radioactive drugs can target only cancer while enhancing safety and effectiveness, leading to recent attention in the pharmaceutical industry.
Similar to the contrast agent, the research team developed a cancer treatment by combining a protein that binds to fibrin with yttrium-90, which emits beta particles. Yttrium-90 is a key ingredient of the radioactive drug Zevalin, which received approval from the U.S. Food and Drug Administration (FDA) in 2022 for the treatment of malignant lymphoma.
After administering the anticancer drug to mice modeled for stomach cancer, the researchers observed the cancer tissue for 20 days. As a result, mice that did not receive any treatment saw a 60% increase in the size of their cancer tissue, while treated mice showed no significant differences. This indicates that the cancer cells were unable to grow because of the attacks from the beta particles emitted by yttrium-90. No significant side effects were noted in treated mice.
Professor Espahani stated, 'The diagnosis and treatment targeting fibrin may also be useful for other cancers with high fibrin content, not just stomach cancer,' and added that it could provide a new option for patients who have developed resistance to traditional radiation therapy.
Reference materials
Science Translational Medicine (2024), DOI: https://doi.org/10.1126/scitranslmed.adn7218