Promising New Concepts for Mesothelioma Treatment
October 1, 2021
Immunotherapy is quickly becoming an essential treatment option for many mesothelioma patients. While it may not yet be an effective therapy for every patient, researchers are working to identify and improve targets for this rare disease.
Since my surgical fellowship at Harvard Medical School and Brigham and Women’s Hospital in Boston, I’ve been focusing my work on understanding the biology and mechanisms of potential new treatments for mesothelioma.
In recent years, we have increased our understanding of mesothelioma and gained new knowledge about mesothelioma genetics, epigenetics, tumor microenvironment and immunobiology.
I believe there is still much to learn about how mesothelioma grows and develops in the body, but every day provides hope that a new piece of information will eventually lead to a cure.
New Immunotherapy Target Shows Promise
In 2021, my team and I published our research on the role of a malignant pleural mesothelioma transcription factor called STAT3.
Transcription factors regulate genes by promoting or suppressing cells’ functions such as division, migration and growth. Many types of tumors activate the STAT3 transcription factor used for the maintenance of new cancer cells.
STAT3 is also responsible for suppressing the local immune response to the area. By inhibiting STAT3, the immune system can more easily destroy cancer cells in the region.
My team was one of the first to experiment with suppressing this factor in mesothelioma using United States Food and Drug Administration-approved drugs: atovaquone and pyrimethamine. Targeting STAT3 led to reduced cancer cell growth and decreased viability.
This target for mesothelioma immunotherapy has great potential. Our data from this study suggested that STAT3 inhibitors could play a vital role combined with immune checkpoint inhibitors or chemotherapy for malignant pleural mesothelioma.
New Concepts Provide Potential for Mesothelioma Treatments
In 2018, my colleagues and I summarized the most recent updates in mesothelioma research for the 14th International Mesothelioma Interest Group conference.
Based on current statistics and promising research, the review focused on potential therapeutic approaches for malignant pleural mesothelioma.
MPM is an aggressive disease with a median overall survival of eight months. The current chemotherapy standard of pemetrexed and cisplatin improves overall survival only 11 weeks compared to cisplatin alone.
Surgery for mesothelioma as part of a multimodality approach remains one of the most effective treatments, but many studies lack evidence for long-term therapeutic benefits.
Immunotherapies are the most promising prospect for these patients, but there is still room for more novel therapies to emerge.
Heparanase Inhibition Slows Tumor Progression
In collaboration with the Israel Institute of Technology and Langone Medical School at the New York University School of Medicine, my research uncovered a potential new therapy using heparanase inhibitors.
Heparanase is part of a process that remodels the extracellular matrix and is associated with tumor metastasis, angiogenesis and inflammation. Angiogenesis is the formation of new blood vessels, which can supply blood and oxygen to a tumor and help it to grow.
In post-surgical patients, high levels of heparanase correlated with reduced survival. As mesothelioma grows within the chest cavity and around the sensitive tissues of the heart and lung, surgery becomes less effective and less beneficial.
After analyzing biopsy and plasma samples from more than 60 patients, we determined that heparanase was highly active in pleural mesothelioma cell lines.
Our research used the drugs PG545 and Defibrotide and determined their ability to restrain mesothelioma tumor growth in mouse models. After examining the mice treated with anti-heparanase, we noticed they developed significantly smaller tumors than the control group.
Notably, the effects caused the cancerous blood vessels to collapse, prohibiting blood flow and increasing local immune cell activity. The median survival of the anti-heparanase mice was 102, nearly double that of mice treated with chemotherapy alone.
The anti-heparanase mice also showed lower rates of cancer proliferation and higher levels of cancer cell apoptosis, the term for programmed cell death. The results strongly encourage further testing, and I’m optimistic that these therapies could become a new standard one day.