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For many rare cancers, early detection and accurate diagnosis have been an ongoing struggle for years. The low incidence rates and often unclear symptoms are just a few factors that can impact a doctor’s ability to recognize these diseases, like diffuse mesothelioma. In more recent years, researchers have made some advancements in diagnostic methods to more accurately and quickly detect even rare cancers.
Mesothelioma has seen new techniques ranging from a breath test that can detect the disease to a variety of biomarkers that can not only potentially lead to earlier diagnosis, but also help doctors determine an effective treatment plan. In a more recent clinical trial, researchers discovered another potential biomarker for diffuse mesothelioma: CD47, sometimes called the “don’t eat me signal.”
CD47 and Diagnosing Diffuse Mesothelioma
Researchers in this study note that often benign reactive mesothelial cells, cells which can be found in the lining or the organs indicating some kind of infection or inflammatory response, may be confused for the malignant cells of diffuse mesothelioma because of their similar cytology. As such, finding the appropriate biomarkers that can better help researchers differentiate between these benign and cancerous cells is essential for early diagnosis. They further noted that some of the biomarkers already used for mesothelioma may have their limits in regard to a longer turnaround time and an expensive detection method, like fluorescence in situ hybridisation (FISH), or even lack sensitivity or specificity in the results.
With this in mind, they sought to find another biomarker that could have more accuracy and sensitivity in the diagnostic process, and also have a more affordable and faster testing method. The study focused on a surface cell protein CD47, also known as integrin-associated protein (IAP). CD47 plays a role in a number of important cell processes, like immune cell activation. Expression of the protein has been found in a variety of cancers, including myeloma and ovarian cancer.
Researchers found that diffuse mesothelioma also showed a high expression of the protein, which could also be used to differentiate the cancerous cells from the benign mesothelial cells. In their analysis, they did note that this protein expression was also largely dependent on the mesothelioma cell type. While patients with epithelioid mesothelioma expressed a high presence of CD47, the study notes that the protein was largely absent or more suppressed in sarcomatoid mesothelioma cell samples.
They further recognize that CD47 along with the presence of the BAP-1 gene in some patients could deliver even more sensitive, accurate results to enable a faster accurate diffuse malignant mesothelioma diagnosis. Researchers found this combination to be the most specific of all the biomarkers that could help lead to a mesothelioma diagnosis.
Developing a Treatment Plan with CD47
Though not an aspect of this particular clinical trial, the researchers stated that expression of this protein could also be an important aspect of developing an effective personalized treatment plan for mesothelioma patients. Researchers noted that CD47 could signal proliferation of tumor cells by stimulating a particular cell pathway. In a controlled setting, the analysts tested if a type of immunotherapy, a monoclonal antibody blocking CD47, could inhibit cancer cell growth and can increase macrophages (a type of white blood cell) having an immune response and consuming the foreign cancer cells.
Immunotherapy treatments like this have shown great promise for mesothelioma and many other cancers already, like lung cancer. Monoclonal antibodies in particular work by binding to specific targets in the body, like CD47, and triggering the immune response that can result in killing the cancer cells. Other monoclonal antibodies have been in development and study for treating mesothelioma, like Keytruda® (pembrolizumab). Keytruda targets another surface protein, PD-1, to ultimately block the growth of cancer cells, and has been found in clinical trials to stop tumor growth and shrink tumors for a number of patients.
There are currently some ongoing early-phase clinical trials further exploring the therapeutic effects of CD47 for mesothelioma, which will hopefully lead to more effective treatments for patients.
The Potential of This Research
Mesothelioma and other asbestos-related diseases have been approached and treated in much the same way for many years, leading to stagnant survival rates and little hope for patients. However, within the last decade especially, survival rates have begun to improve, especially for peritoneal mesothelioma. With new treatments and better diagnostic techniques, over half of diffuse peritoneal mesothelioma patients are surviving 5 years or longer.
Finding another biomarker like CD47 can have a great impact on further improving survival rates for both peritoneal and malignant pleural mesothelioma, especially if it can also be targeted with future immunotherapy treatments. Conventional treatments like surgery, which can include the rather risky extrapleural pneumonectomy for pleural mesothelioma patients, and chemotherapy drugs like pemetrexed can be too aggressive for some patients to handle.
Other patients who have limited treatment options and don't see progress from these standard therapies may sometimes only be left with palliative options to relieve pain and other symptoms. Immunotherapy has shown promise in clinical trials even for mesothelioma patients at more advanced stages of disease as a safe, effective, and tolerable treatment. Finding a new potential target for another immunotherapy treatment with CD47 can have a huge, positive impact for many patients.