Written By: Devin Golden
Mesothelioma Tumors
Mesothelioma tumors aren’t like those of other cancers. They spread through the body in a unique way, which explains why mesothelioma is difficult to stop. It’s also why mesothelioma survival rates are low.
Medically Reviewed By
Karen Ritter, RN BSN
Registered Nurse
Medically Reviewed By
Karen Ritter, RN BSN
Registered Nurse
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Important Facts About Mesothelioma Tumors
- Mesothelioma tumors are clumps or buildups of mesothelial cells. They form when mesothelial cells mutate due to sharp asbestos fibers piercing the cell linings.
- Mesothelioma tumors proliferate in the body in an unorthodox way. The original tumor grows and spreads, but separate tumors also form. The disease looks like scattered bumps.
- Two signal pathways are disrupted, leading to tumors. They are Vascular Endothelial Growth Factor and Epidermal Growth Factor Receptor. They create new blood vessels and control cell division.
- Research is underway to find tumor-suppressing drugs for mesothelioma. The therapy should focus on the tumors’ unique characteristics.
What Are Mesothelioma Tumors?
Mesothelioma tumors are overproduced clumps of mesothelial cells. These cells line each side of the pleura and peritoneum, which are protective linings near vital organs. Mesothelioma tumors form due to asbestos fibers irritating mesothelial cells.
The pleura is a narrow membrane separating the chest wall and lung cavity. The peritoneum is a thin lining encompassing the abdominal cavity. These two areas are where the two main types of mesothelioma — pleural mesothelioma and peritoneal mesothelioma — arise.
There are two types of mesothelioma tumors: malignant and benign. Malignant mesothelioma tumors actively replicate and spread within the body. They are dangerous to tissue and organs. Benign mesothelioma tumors are dormant, or not active Therefore, they are not cancerous.
Most research and discussion involving mesothelioma focuses on malignant tumors.
Attributes of Mesothelioma Tumors
Malignant mesothelioma tumors develop in an unorthodox manner, and treatment is often limited. This is because of the:
- Number of tumors — Mesothelioma is made up of many microscopic tumors rather than one large tumor.
- Growth — These tumors grow in size but remain relatively small compared to tumors of other types of cancer.
- Angiogenesis and hypoxia — Mesothelioma cells create new blood vessels, which supply them with blood and oxygen needed to grow. This phenomenon also prevents healthy cells from receiving nutrients.
- Spreading mechanism — These tumors continue replicating and forming new clumps of cells. This leads to an unorthodox spreading within the body called mesothelioma metastasis.
- Difficulty to remove — Surgery is the most effective way to remove mesothelioma tumors. However, since the tumors are small in size and countless in quantity, complete removal is challenging. Surgery often leaves a few scattered, remnant tumors in the body.
How Do Mesothelioma Tumors Form?
Mesothelioma tumors form from exposure to asbestos. Inhaling or ingesting microscopic asbestos fibers causes genetic changes to the body’s mesothelial cells.
Asbestos fibers are sharp enough to puncture mesothelial cells in the pleura or peritoneum. This causes irritation, which leads to cell mutation and replication. This uncontrolled duplication leads to batches of cells, which is a mesothelioma tumor.
How Do Malignant Mesothelioma Tumors Grow and Stay Alive?
The immune system usually attacks infections and diseased cells. Healthy cells go through a natural life cycle ending with “programmed cell death.” The cells comprising malignant mesothelioma tumors have unique characteristics allowing them to avoid death and grow without the immune system’s opposition.
Challenge for the Immune System
The body’s natural defense, the immune system, attempts to fight mutated mesothelial cells. However, mesothelioma cells have features preventing the immune system from controlling the cancer naturally.
First, they duplicate at an abnormally rapid pace even for cancer. This overwhelms the immune system. Rather than one tumor to focus on, the immune system is concerned with many microscopic tumors spreading in a unique way.
The disease proliferates like “a sheet” or “an avalanche,” as described by Dr. Raja Flores, the director of thoracic surgery at New York City’s Mount Sinai Medical Center. As the scope of the cancer widens and expands, the immune system struggles to control it.
Second, mesothelioma cells have protein receptors helping them hide from the immune system. Examples of these receptors are:
- PD-L1 — When this protein connects with the T-cells’ PD-1 receptor, the T-cells mistake mesothelioma cells as healthy and harmless.
- B7 — This protein, like PD-L1, is an immune checkpoint. It subdues the immune system’s cancer-fighting white blood cells.
Numerous clinical trials are investigating mesothelioma immunotherapy drugs to block these protein receptors. Researchers hope the drugs can help the immune system function appropriately. Examples of these drugs are nivolumab, pembrolizumab, durvalumab and ipilimumab.
With no immunotherapy
PD-1 on the T-cell binds with PD-L1 on the cancer cell, the T-cell's immune system functioning shuts down and cancerous cells can roam freely in the body.
With immunotherapy
Nivolumab blocks the binding of PD-1 and PD-L1, thus allowing the T-cell to effectively identify and target intruding mesothelioma cancer cells.
Signal Pathways and Growth Factors
When mesothelial cells become cancerous, their DNA is damaged. The harm to cellular DNA changes the signaling pathways cells use to communicate with each other. These signal pathways, controlled by proteins, turn into growth factors for mesothelioma.
Two proteins play a large part in affecting signal pathways and helping malignant mesothelioma tumors grow:
- Vascular Endothelial Growth Factor (VEGF), which stimulates the creation of new blood vessels
- Epidermal Growth Factor Receptor (EGFR), which controls cell division and survival
VEGF in Mesothelioma
Like all cells, the ones comprising mesothelioma tumors need a consistent blood and oxygen supply. Blood vessels feed tumors with nutrients to continue growing.
Mesothelioma cells can produce new blood vessels, a biological process known as “angiogenesis.” This process is caused by VEGF, a signal protein produced by cells. Mesothelioma cells often have a high amount of VEGF. These new blood vessels feed the malignant mesothelioma tumors, which grow and invade nearby tissue and organs.
Without a supply of blood and oxygen, malignant mesothelioma tumors can’t grow. The same is true for healthy cells, and angiogenesis can deprive healthy cells of consistent blood and oxygen. This can lead to cellular death, called “hypoxia.”
Doctors are developing anti-VEGF drugs to prevent angiogenesis, which can kill mesothelioma cells and protect healthy ones. For instance, drugs like ramucirumab and bevacizumab block the creation of new vessels. This leads to hypoxia for mesothelioma cells.
Early Mesothelioma Tumor Development
EGFR in Mesothelioma
Signaling pathways let cells know when to stop multiplying and finally undergo “apoptosis,” which is cell death. The body needs cells to routinely commit apoptosis. This keeps the body healthy, as cells that do not commit apoptosis can become virus-infected. It also keeps the body balanced with an appropriate amount of cells.
Mesothelioma cells avoid apoptosis due to the EGFR protein, which monitors cell division and apoptosis. Mesothelioma cells have a higher amount of EGFR, which leads to more rapid growth and prevents cellular death.
This leads to a cellular imbalance in the body, as the diseased cells continue replicating but do not die off. The diseased cells invade tissue and organs by outnumbering the healthy cells, which continue to regulate themselves through apoptosis.
Limits in Mesothelioma Surgery
The goal of mesothelioma surgery is to remove as much of the disease as possible. Removing all malignant mesothelioma tumors is challenging due to their nature.
Mesothelioma is sometimes referred to as “diffuse malignant mesothelioma” because the tumors are microscopic and dispersed. The term “diffuse” means spread out over a large area.
While tumors for most other cancers start inside of organs, containing them to one area, mesothelioma tumors form in tissue linings. The tumors easily duplicate and scatter throughout the body by escaping these linings, reaching organ cavities and eventually organs themselves. They are less contained, which makes complete removal during surgery more difficult.
How Treatment Is Advancing to Improve Mesothelioma Survival
Mesothelioma specialists often pair surgery with other treatment options, such as chemotherapy, radiation and immunotherapy. Doing so can address remnant, scattered tumors.
There are three aggressive, possibly life-saving surgeries for mesothelioma:
- Extrapleural pneumonectomy (EPP), for pleural mesothelioma
- Pleurectomy with decortication (P/D), also for pleural mesothelioma
- Cytoreduction with heated intraperitoneal chemotherapy (HIPEC), for peritoneal mesothelioma
EPP is the original pleural mesothelioma surgery and is more aggressive. It removes the affected lung, in addition to the pleura and other areas or tissue overrun with tumors.
P/D is a newer surgical option, and it is becoming the primary choice among specialists. It spares the lung and removes the pleura, diaphragm and possibly the pericardium (which lines the heart). P/D usually has fewer complications than EPP.
Cytoreduction with HIPEC involves \”debulking,\” which is removal of visible tumors from the peritoneum and abdominal cavity. The surgery also removes the peritoneum, the thin lining around the abdomen. A heated, liquid chemotherapy, HIPEC, goes directly into the cavity to wash out the remaining microscopic tumors.
Mesothelioma survival time continues improving with the advancement of treatment. Researchers are gaining a better understanding of mesothelioma tumors, including how to stop their growth and replication. You can learn more about this disease and how it’s treated with our free Complete Mesothelioma Guide book.
Sources & Author
- Malignant Mesothelioma Treatment. National Cancer Institute. Retrieved from: https://www.cancer.gov/types/mesothelioma/patient/mesothelioma-treatment-pdq#section/all. Accessed: 05/18/2020.
- Neoadjuvant Immune Checkpoint Blockade in Resectable Malignant Pleural Mesothelioma. Clinicaltrials.gov. Retrieved from: https://clinicaltrials.gov/ct2/show/NCT03918252. Accessed: 05/14/2020.
- Angiogenesis Inhibitors. National Cancer Institute. Retrieved from: https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/angiogenesis-inhibitors-fact-sheet. Accessed: 05/18/2020.
- Combined inhibition of MET and EGFR suppresses proliferation of malignant mesothelioma cells. Division of Molecular Oncology, Aichi Cancer Center Research Institute. Retrieved from: http://carcin.oxfordjournals.org/content/30/7/1097.full.pdf. Accessed: 10/10/18.
- Apoptosis. Khan Academy. Retrieved from: https://www.khanacademy.org/science/biology/developmental-biology/apoptosis-in-development/a/apoptosis. Accessed: 05/18/2020.
- WDefinition of epidermal growth factor receptor. National Cancer Institute. Retrieved from: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/epidermal-growth-factor-receptor. Accessed: 05/18/2020.
- Vascular Endothelial Growth Factor. University of Rochester Medical Center. Retrieved from: https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=167&contentid=vegf. Accessed: 05/18/2020.
