Mesothelioma tumors aren’t like those of most other cancers. They spread through the body in a unique way, one which helps explain why mesothelioma is difficult to treat and escalates so quickly.
Written by Jenna Campagna, RN
What Are Mesothelioma Tumors?
Mesothelioma tumors are clumps of cancer cells that derive from healthy 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 these mesothelial cells.
The pleura is a narrow membrane separating the chest wall and lung cavity. The peritoneum is a thin lining that encompasses 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 are active in replicating and spreading within the body. They are dangerous to tissue and organs. Benign mesothelioma tumors are dormant, or not active and thus not cancerous.
Most research and discussion involving this cancer focuses on malignant mesothelioma tumors.
Attributes of Mesothelioma Tumors
Malignant mesothelioma tumors have numerous attributes that explain how the cancer develops and why treatment is often limited:
- 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.
- Difficult 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 years after exposure to asbestos. Inhaling or ingesting microscopic asbestos fibers causes changes in the genetic makeup of healthy mesothelial cells.
How Do Malignant Mesothelioma Tumors Grow and Stay Alive?
Infected cells are usually attacked by the immune system, and healthy cells go through a natural life cycle that eventually leads to “programmed cell death.” The cells that comprise malignant mesothelioma tumors have unique characteristics that allow them to avoid these occurrences and grow without opposition.
Challenge for the Immune System
The body’s natural defenses, such as the immune system, attempt to fight these mutated mesothelial cells. However, mesothelioma cells have features that prevent the immune system from controlling the cancer naturally.
First, these cancerous cells duplicate at a rapid pace that overwhelms the immune system. Rather than one tumor to focus on, the immune system must focus on many microscopic tumors that spread 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.
Second, mesothelioma cells have protein receptors that help them hide from or inhibit the immune system. Examples of these receptors are:
- PD-L1 — When this receptor connects with the T-cells’ PD-1 receptor, the T-cells mistake mesothelioma cells as healthy and harmless.
- CTLA-4 — This receptor, 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 that block these protein receptors. Researchers hope that the drugs can help the immune system function appropriately and label mesothelioma cells as dangerous. Examples of these drugs are nivolumab, pembrolizumab and ipilimumab.
Signal Pathways and Growth Factors
When mesothelial cells become cancerous, their DNA is damaged. The harm to cellular DNA also causes change to the signaling pathways used by cells to communicate with each other. These signal pathways, which are controlled by proteins, turn into growth factors for mesothelioma.
There are two proteins that 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 to flourish. Blood vessels feed tumors with nutrients needed to continue growing.
Mesothelioma cells can produce new blood vessels, a biological process known as “angiogenesis.” This process is caused by VEGF, which is 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 continue to grow and invade nearby tissue and organs.
Without a supply of blood and oxygen, malignant mesothelioma tumors don’t have the essential nutrients to continue growing. The same is true for healthy cells, and angiogenesis can deprive healthy cells of consistent blood and oxygen. This can lead to cellular death, which is called “hypoxia.”
Doctors are currently developing anti-VEGF drugs to inhibit 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 explicitly for mesothelioma cells.
EGFR in Mesothelioma
Signaling pathways also let cells know when to stop multiplying and finally undergo “apoptosis,” which refers to cellular death. The body needs cells to routinely commit apoptosis to remain healthy, as cells that do not commit apoptosis can become virus-infected.
Mesothelioma cells avoid apoptosis due to the change in 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 naturally die off. The diseased cells invade tissue and organs by outnumbering the healthy cells, which continue to regulate themselves and commit apoptosis.
Limits in Mesothelioma Surgery
The goal of mesothelioma surgery — or surgery for any type of cancer — 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, which contain them to one area, mesothelioma tumors form in protective tissue linings. The tumors more easily duplicate and scatter to tissue throughout these linings, into 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 even immunotherapy. Doing so can address the remnant, scattered tumors not removed during surgery.
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 involves removing the affected lung, in addition to the pleura and other areas or tissue overrun with pleural mesothelioma tumors.
P/D is a newer surgical option than EPP, and it is becoming the primary option among specialists. It spares the lung and focuses on removing the pleura, diaphragm and possibly the pericardium (which lines the heart). P/D usually has fewer complications.
Cytoreduction with HIPEC involves “debulking,” which is removal of visible tumors from the peritoneum and abdominal cavity. A heated, liquid chemotherapy, HIPEC, is then administered directly into the cavity to focus on the remaining microscopic tumors.
Mesothelioma survival time continues to improve with the advancement of treatment techniques. Researchers continue to gain 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.
Last Edited: August 3, 2020.