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Mesothelioma Research

Mesothelioma research plays a crucial role in developing new and effective treatments for the cancer. New clinical trials and emerging treatments may be able to significantly extend life expectancies for mesothelioma patients and are a result of continued research.

In the 1960s, just over 200 asbestos- and mesothelioma-related articles were published. Within the year 2018, more than 7,000 mesothelioma-related articles have been published. With a continued rise in mesothelioma diagnoses throughout the last decade, mesothelioma experts continue to look for new treatments, a cure and a better understanding of the disease.

The Importance of Mesothelioma Research

Mesothelioma is a rare cancer that has around 3,000 newly diagnosed cases in the United States each year. Due to its rarity, there isn’t as much data around mesothelioma as there is for other, more common cancers, such as lung cancer. Malignant mesothelioma research plays a crucial role for patients for a variety of reasons.

Improved Diagnostic Tools

Early detection can strongly influence prognosis for mesothelioma patients. If the disease is caught in the early stages, more treatment options are available. Treatments can also be more aggressive, and patients typically face better survival rates than those diagnosed at stage 3 or stage 4.

Blood Tests and Biomarkers

One of the largest improvements in diagnostic tools has been blood tests and biomarkers. Researchers continue to find biomarkers, or substances in the blood, that can suggest a mesothelioma diagnosis, show symptoms of mesothelioma or demonstrate a history of asbestos exposure, the only known cause of the disease. One of the newest biomarkers is HMGB1, with one study distinguishing between those with mesothelioma, those with a history of asbestos exposure but no mesothelioma and those with a history of asbestos exposure with mesothelioma. While blood tests cannot diagnose the cancer on their own, they can prompt physicians to conduct imaging scans and biopsies.

Mesothelioma Breath Test

Researchers continue to look for improved early diagnostic tools, one of which has been a mesothelioma breath test. More research is required, but a collection of case studies has found that the gas chromatography-mass spectrometry is a component of the breath test that can differentiate between at-risk, asbestos-exposed individuals and malignant pleural mesothelioma patients with 97% accuracy.

Emerging Treatments and Clinical Trials

Most malignant mesothelioma patients face survival of less than one year. However, advancements in treatment offer hope in improving prognosis. Before becoming a first-line treatment option, newer treatments are tested in clinical trials. Patients must meet certain criteria to participate, but clinical trials are often an option for those not responding to the standard of care. If successful, clinical trials have the potential to gain FDA approval and status as a first- or second-line treatment option.

Newer treatments that have shown some success include gene therapy, immunotherapy and photodynamic therapy. Photodynamic therapy, in particular, has been a focus of many recent studies, showing success in extending survival of stage 3 patients to up to 7.3 years after diagnosis when used intraoperatively, in combination with surgery and chemotherapy.

Improved Standard Treatments

Advancements have also been made to existing standards of care, including surgery, chemotherapy and radiation, and how they are used together. Mesothelioma specialists continue to test and improve efficacy of these treatment plans.

Chemotherapy and Immunotherapy

The National Comprehensive Cancer Network (NCCN) recently updated their guidelines to include a combination of Alimta, cisplatin and bevacizumab as a first-line treatment, combining chemotherapy drugs with an immunotherapy drug. The NCCN recognizes that this is only an option for patients not eligible for surgery. In a recent study of 448 patients, half treated with all three drugs and half treated without bevacizumab, overall survival improved for those treated with the full combination. The combination of three extended survival to 18.8 months on average, while the combination of just Alimta and cisplatin had an average survival of 16.1 months.

Resources for Mesothelioma Patients and Their Families

Curative Radiation Therapies

Researchers of radiotherapy and mesothelioma have also looked into how it can be used curatively. Studies have shown that Surgery for Mesothelioma After Radiation Therapy (SMART) with intensity-modulated radiation therapy has been able to extend survival to 51 months, on average. This treatment plan begins with radiation therapy and follows with surgery, often an extrapleural pneumonectomy. Researchers and advocates of SMART continue to try and improve the efficacy of this option, also finding success in the combination of radiation therapy and immunotherapy prior to surgery.

Improved Palliative Care

Palliative care plays an important role in mesothelioma treatment, helping reduce symptoms for patients. As cancer cells spread throughout the body, patients typically experience more symptoms, as well as side effects from treatments. Palliative care can offer symptomatic relief and a higher quality of life.

Mesothelioma case studies continue to analyze the effectiveness of particular palliative treatments for both mesothelioma patients and mesothelioma survivors. For example, recent studies have looked into the palliative effects of radiation therapy on pleural mesothelioma patients. In one study, palliative radiotherapy was reported to help with pain management and improve quality of life for 50 – 60% of mesothelioma patients. Researchers continue to look into how radiation therapy can be used palliatively on its own and in combination with other treatment techniques.

Understanding Mesothelioma

Pleural mesothelioma is the most common type, making up around 80 – 90% of all cases, followed by peritoneal with 15 – 20%, pericardial with 1 – 2% and testicular mesothelioma with less than 1%. There are also rare cell types that affect even fewer individuals. Case studies most commonly cover malignant pleural mesothelioma, but research is still limited.

As more cases of mesothelioma emerge, new case studies are conducted and the number of cases analyzed increases, researchers can better understand mesothelioma statistics, cancer progression, successful treatments, risk factors and other information that will improve the diagnosis and treatment of the disease.

Mesothelioma and Genetics

One study of interest is genetics and mesothelioma. Studies throughout the past decade have looked into how genetics may be able to identify individuals that are more at risk to develop mesothelioma and other asbestos cancers. During histology, specialists can look at patient DNA to observe chromosomal losses and gains, pinpointing connections in cases of patients with malignant mesothelioma. More research is needed to determine their efficacy in assisting with diagnosis and prognosis of the disease.

The BAP1 gene is a tumor suppressor gene that has shown links to pancreatic cancer, ovarian cancer, breast cancer and malignant mesothelioma. Studies have found a large number of malignant mesothelioma cases have demonstrated mutation of the BAP1 gene. One recent study looked at both benign and malignant mesothelioma tumors and was able to detect malignancy with 100% accuracy using a BAP1 immunostain, offering much promise to help with early detection. Over the past few years, researchers have also seen a connection with BAP1 gene mutations and prognosis, demonstrating poor survival in mesothelioma patients with no gene expression, though more research is needed.

Along with other types of cancer, p53 gene loss has assisted with detection of malignancies and research for a cure continues to look into how repairing damages to the gene sequence may be able to help treat the disease. Another study took pleural fluid samples from a series of patients and found a loss of chromosome 9 expression (CDKN2A/ARF) in 72% of mesothelioma cases and a deletion of 9p in all cases of patients that had a history of asbestos exposure, suggesting that these genes can help identify patients that are at-risk of developing the disease.

Chromosomal Losses Linked to Mesothelioma
  • BAP1
  • Chromosome 14q
  • Chromosome 13q
  • Chromosome 11q23
  • Chromosome 4q
  • Chromosome 6q
  • Chromosome 22q (NF2 and Merlin protein)

The Need for Continued Mesothelioma Research

Diagnostic tools and treatment options for mesothelioma, as well as understanding of the disease have improved throughout the years. However, there is still a large need for more data, tools to help with early detection, better treatment options and a cure for the cancer, stressing the importance of continued mesothelioma cancer research.

Research is crucial not just for physicians when addressing and treating the disease, but for patients and their loved ones seeking to better understand their diagnosis, treatment options and prognosis.

The mesothelioma community is comprised of many survivors, patients, loved ones, specialists, researchers, organizations and foundations dedicated to raising awareness of the disease and funding to continue research efforts.

Selected Mesothelioma Research Studies

Author: Linda Molinari

Editor in Chief, Mesothelioma Cancer Alliance

Linda Molinari

Reviewer: Annette Charlevois

Patient Support Coordinator

Annette Charlevois
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Sources

Betrouni N, Munck C, et al. Real-time light dosimetry for intra-cavity photodynamic therapy: Application for pleural mesothelioma treatment. June 2017;18:155-161. doi: 10.1016/j.pdpdt.2017.02.011

Brusselmans L, Arnouts L, et al. Breath analysis as a diagnostic and screening tool for malignant pleural mesothelioma: a systematic review. Translational Lung Cancer Research. October 2018; 7(5).

Cigognetti M, Lonardi S. BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations. Modern Pathology. August 2015;28(8):1043-1057. doi: 10.1038/modpathol.2015.65

Friedberg JS, Simone CB II, et al. Extended Pleurectomy-Decortication–Based Treatment for Advanced Stage Epithelial Mesothelioma Yielding a Median Survival of Nearly Three Years. The Annals of Thoracic Surgery. March 2017;101(3):912-919. doi: 10.1016/j.athoracsur.2016.08.071

Mineo TC. Malignant Pleural Mesothelioma: Present Status and Future Directions. February 2016.

National Comprehensive Cancer Network. Malignant Pleural Mesothelioma. 2016:Version1.2016.

Pulford E, Huilgol K, et al. Malignant Mesothelioma, BAP1 Immunohistochemistry, and VEGFA: Does BAP1 Have Potential for Early Diagnosis and Assessment of Prognosis? Disease Markers. 2017;2017:1310478. doi: 10.1155/2017/1310478

Yang H, Pass H and Carbone M. OA22.03 HMGB1, a Target for Mesothelioma Therapy and a Biomarker to Detect Asbestos Exposure and to Identify Mesothelioma Patients. January 2017;12(1):S330–S331. doi: 10.1016/j.jtho.2016.11.356

Zalcman G, Mazieres J, et al. Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. The Lancet. April 2016;387(10026):1405-1414. doi: 10.1016/S0140-6736(15)01238-6

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