High Mobility Group Box Protein-1 (HMGB1) is a mediator between asbestos-related inflammation and the development of mesothelioma. Monitoring these levels can help identify people with asbestos exposure, which could increase screening and treatment options.
What Is HMGB1?
High mobility group protein B1 (HMGB1), also known as amphoterin, is a protein secreted by the human body in response to inflammation. Heightened levels of HMGB1 often indicate autoimmune dysfunction. Several illnesses can cause immune dysfunction, including lupus, arthritis, and cancer.[1]
Not only is HMGB1 more prominent in mesothelioma patients, but it also seems to play a role in keeping the cancer growing.
Mesothelioma and Asbestos
Malignant mesothelioma is a rare and aggressive cancer that typically affects the lungs (pleural mesothelioma), heart (pericardial mesothelioma), or abdominal cavity (peritoneal mesothelioma). In rare cases, mesothelioma develops in the testicles.
Asbestos exposure is the most significant risk factor for mesothelioma. It is typically associated with long-term exposure. Because asbestos was once commonly used in the construction industry, many mesothelioma victims spent a lifetime installing asbestos-containing tiles, insulation, and other products.
The time from initial exposure to diagnosis is lengthy compared to other cancers. Sometimes, a person afflicted with mesothelioma will not notice symptoms until several decades after the exposure.
What Is Immunotherapy?
Immunotherapy is a form of systemic therapy that uses the body’s immune system to “attack” cancer cells. It is a developing mesothelioma treatment that helps some patients live longer.
Unfortunately, cancer often can grow undetected by the immune system. Immunotherapy aims to help the immune system identify cancerous cells and stop their growth.
There are several types of immunotherapy, which include immune checkpoint inhibitors, T-cell transfer therapy, monoclonal antibodies, and vaccinations. They are either given intravenously or by injection.[2]
What Happens with HMGB1 in Mesothelioma Patients?
HMGB1 is secreted at higher levels in mesothelioma patients than in other individuals. Researchers initially thought the high level of the protein was an immune response to cancer. This would indicate cancer caused the excessive release of the HMGB1 protein.
Researchers have found that HMGB1 could act like a master switch that turns asbestos-damaged cells in the body into cancer cells.[3]
The research suggests a connection between HMGB1 secretion and cancer progression.[3] In other words, HMGB1 appears to “feed” the malignant cells; therefore, HMGB1 not only increases as cancer spreads but also helps spread the cancer in a feedback loop.
HMGB1 and Mesothelioma Immunotherapy
Currently, no approved treatments exist that specifically target HMGB1. However, ongoing research and clinical trials are being conducted for several cancer types.
Preventing Mesothelioma After Asbestos Exposure
One important idea is that targeting HMGB1 could delay the onset of mesothelioma in people at risk for it. This would include people with a family history and past asbestos exposure. If HMGB1 is, in fact, necessary for turning healthy cells into cancer cells, it could potentially prevent mesothelioma.[3]
Slowing the Progression of Mesothelioma
Research has found that targeting HMGB1 via immunotherapy could impact the spread of malignant mesothelioma. Since HMGB1 appears to increase the proliferation and spread of cancer cells, the idea is to inhibit HMGB1’s production through the use of lab-created antibodies.[4]
HMGB1 has also been found to help mesothelioma migrate in the body. The cancer may even need it to survive. When malignant mesothelioma cells are deprived of HMGB1 via immunotherapy, they cannot spread.
This type of treatment does not target cancer, but targets the HMGB1 instead, which affects the cancer in turn. In mice studies, HMGB1 inhibition therapy helped halt tumor growth and the mice subsequently lived longer.
Aspirin and HMGB1
Aspirin (acetylsalicylic acid) is an anti-inflammatory medication. Aspirin has some anti-cancer effects and has been shown to limit the spread and reduce mortality of some cancers, specifically those mediated by inflammation.
Researchers used animal models to determine if aspirin mediates HMGB1 and could therefore limit the spread of mesothelioma. They found that clinical doses of aspirin improve survival rates in laboratory animals with mesothelioma. More research is needed in human patients.[5]
HMGB1 as a Marker to Diagnose Mesothelioma
Research into HMGB1’s role in mesothelioma may even change how the cancer is diagnosed. A small study found it to be a sensitive biomarker.
It may help provide more accurate, earlier diagnoses by distinguishing between patients with asbestos exposure and mesothelioma and those with no disease or another disease.[6]
HMBG1 and the Future of Mesothelioma Treatment
Because mesothelioma spreads rapidly, it can have devastating consequences if it is not caught early. Unfortunately, many people do not notice the signs and symptoms until it has already done extensive damage to the body. This is why early diagnosis and effective treatment are crucial.
Although it may not completely eradicate cancer, HMGB1-inhibiting antibodies in immunotherapy could help those with malignant mesothelioma live longer lives by halting cancer cell growth.
Preventing metastasis (where cancer travels from its original location to affect distant parts of the body) is key for improving mesothelioma prognoses. Additional research and clinical trials are ongoing to help bring more treatment options to patients.
