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Mesothelioma treatment

First New Mesothelioma Therapy Approved by FDA in Over 15 Years

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The first new mesothelioma therapy approved by the FDA is based on a trial. In this single-arm STELLAR trial, the median overall survival rate was 18.2 months with patients with unresectable, locally advanced or metastatic malignant pleural mesothelioma who received TTF plus chemotherapy. This combination of treatments comprises the NovoTTF-100L System along with pemetrexed and platinum-based chemotherapy for front-line treatment.

History of new mesothelioma therapy

Bill Doyle, executive chairman of Novocure, the developer of NovoTTF-100L stated, “Since 2000, we have been developing and commercializing Tumor Treating Fields (TTF) to extend survivals in some of the most aggressive forms of cancer. FDA approval of NovoTTF-100L provides patients with the first FDA-approved treatment for MPM in more than 15 years and, as our first FDA-approved torso cancer indication, marks a major milestone for Novocure. We are thankful for the patients, caregivers and health care providers who partnered with us to make this possible.”

What is malignant pleural mesothelioma (MPM)?

Strongly linked to asbestos exposure, MPM is a rare malignancy. Approximately 3,000 people are diagnosed with MPM each year in the US. This new therapy is welcome news as there was only one FDA-approved therapy prior to the NovoTTF-100L approval. That treatment consisted of pemetrexed plus cisplatin.

In addition to extending life, this new mesothelioma therapy approved by the FDA, is noninvasive, delivering TTF directly to the region of the tumor. No increase in serious systemic wide effects were noted with this new therapy.

Results showed patient overall survival at:
• 21.2 months for epithelioid malignant pleural mesothelioma (53 patients)
• 12.1 month for non-epithelioid malignant pleural mesothelioma (21 patients)
• 62% of those in the STELLAR study were alive at one year.
• Disease control when at least one CT scan was given as a follow-up was 97% (72 patients).

Mary Hesdorffer, NP, executive director of the Mesothelioma Applied Research Foundation, said “MPM is a devastating disease, with only 10 to 20 percent of patients being candidates for surgery to remove the tumor. Typically, mesothelioma patients who cannot have surgery receive palliative care to mitigate their symptoms. NovoTTF-100L provides unresectable MPM patients with a treatment option that may improve survival. We are encouraged by the FDA approval and hope it is just the beginning of innovation in the treatment of this aggressive disease.”

Studies Continue in Search of a Mesothelioma Cure

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Mesothelioma is a disease primarily caused by asbestos exposure and is usually fatal within a short period of time, however studies continue in search of a mesothelioma cure. This is not a simple task, as researchers are still not sure of the reason asbestos fibers encourage cancer in some individuals. With the long latency period between exposure and diagnosis, people will be fighting this disease for many decades to come. That means that new treatments to defeat the disease are urgently needed.

In the past, and currently, treatments often consisted of chemotherapy, radiation therapy, or surgery. These have extended the lives of many patients and they still do. However, as noted by the American Cancer Society, there are new studies and treatments that carry the promise that they may do more than extend life for a few months and actually bring about a cure.

What are the latest treatments?

While there are treatments currently in use, they are often limited in their effect and generally extend life a little longer rather than cure the disease. New ideas and studies take place all the time. Some of the newest treatments still under testing are listed below.

Immunotherapy

Clinical trials are underway using a patient’s own immune cells to attack their cancer. These cells are removed from the blood, taken to the lab where they are manipulated to react to tumor cells. They are then put back into the patient’s body through a blood transfusion. The presumption is these transformed immune cells will encourage the patient’s immune system to kill the cancer cells.

One other immunotherapy in trials uses tremelimumab, a drug that encourages the immune system to attack full force as it targets specific immune cells.

Gene therapy

This innovative treatment uses modified viruses and injects them into the cancer cells. Once an infection is created, the virus introduces new selected genes into the cells, which makes the cells easier to destroy. In some tests, the gene present in the virus assists in turning on the immune system to attack the cancer cells.

Virus therapies

Still in the early stages of testing, a specially created virus is put into the pleural space of the cancer cell. In the desired outcome, the virus would directly infect and then kill the cancer cells, or indirectly, the immune system would be encouraged to kill the cancer cells.

Targeted drugs

While chemotherapy has been used for some time but with limited success, there are newer chemotherapy drugs in tests that may do much more. These drugs are targeted to a specific type of cell or protein instead of standard chemotherapy that affects the whole body. This means there are usually fewer side effects.

Photodynamic therapy

While it sounds futuristic, there are a number of clinical trials in process that study the use of photodynamic therapy (PDT). Veins are injected with a light-activated drug. Once in the body, it spreads into cancer cells throughout the body. After a few days, a tube with a special red light on the tip is placed into the chest, usually after a surgery. The drug is activated by the light producing a chemical change that kills the cancer cells. Because all this happens only within the cancer cells, there may be fewer side effects.

Encouraging progress

The knowledge that studies continue in search of a mesothelioma cure should be an encouragement to anyone diagnosed with the disease or who have a experienced extended exposure to asbestos. Contact your doctor or this link to view current trials and, perhaps, find a new trial that interests you. There is hope, and we need to support those who are researching for ways to combat and kill mesothelioma before it continues its deadly toll.

Innovative Study that Inhibits Cancer Metastases

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Researchers at Case Western Reserve University School of Medicine, the National Cancer Institute, and Cleveland Clinic, as well as four other institutions, conducted an innovative study that inhibits cancer metastases through the use of epigenetics.

Epigenetics is the key

Epigenetics is the “study of biological mechanisms that will switch genes on and off.” That is an extremely simplified explanation, but that is the method used by these researchers. In the study, bone cancer (osteosarcoma) cells were halted in their spread to the lungs of mice. This is a major triumph as there is presently no widespread, approved and targeted anti-metastatic therapy for the disease. If metastases is prevented, fatalities from cancers can be reduced significantly.

Peter Scacheri, professor of genetics and genome sciences at Case Western Reserve University School of Medicine and member of the Case Comprehensive Cancer Center stated, “More than 90 percent of all cancer deaths are the result of tumor metastasis, not primary-site tumors. While many of the genes responsible for metastasis have been identified, the mechanisms that control these genes are not well defined. Our findings demonstrate that altered gene-enhancer activity is fundamental to a cancer cell’s ability to metastasize.”

These gene-enhancers, actually short segments of DNA, act like switches to activate genes. This is a necessary process for normal development. There are tens of thousands of these in a single cell! Sometimes, however, the process goes awry and contributes to the formation and spreading of tumor cells. This study showed that the on-off switches of metastasized cancer cells are in different positions than those in the primary tumor.

The experiment to inhibit cancer metastases

The researchers consistently noticed certain bunched groups of enhancers (metastatic variant enhancer loci – Met-VELs) were close to cancer genes in the lung metastases of patients with osteosarcoma. This indicated that were crucial to the metastatic process. They then saw that osteosarcoma cell growth in the lung can be diminished with BET inhibitors (current anti-cancer drugs in clinical trials). These interrupt the Met-VELs function in influencing gene expression. They also found that a certain Met-VEL-linked gene, Tissue Factor (F3), must be present for metastatic colonization. This interruption of signaling and the blood clotting factors of F3 prevented metastasis.

“Our experiments show that removing a single enhancer of the F3 gene in tumor cells virtually eliminates their ability to metastasize in mice,” said Scacheri. “Collectively, our findings establish that enhancer elements endow tumor cells with metastatic capacity and that targeted inhibition of genes associated with enhancer alterations, or deleting altered enhancers themselves is sufficient to block metastatic colonization and proliferation. While our work focused on lung metastasis in osteosarcoma, the findings have implications for other types of metastatic cancer as well.”

The benefits

This experiment changes the way researchers look at stopping cancer metastasis. Most research focused on gene mutation, not how – or even if – specific genes could be turned off or on. Studies in how tumors are formed and the differences in cancer cells versus normal cells has also been a primary area of study – usually in the early stages of a disease. At that point, treatment generally targets primary tumors, not those cancer cells that have traveled elsewhere in the body.

With this study, an entirely new treatment possibility may exist. This may not only affect osteosarcoma metastasizing to the lungs, but may mean the primary tumors of other cancers will be stopped before invading secondary areas of the body. This could be a new way to tackle the spread of mesothelioma and give hope to those diagnosed with this fatal disease.

The knowledge and creativity of scientists and researchers worldwide must be applauded as they continue to develop new and more effective treatments for cancers and other devastating diseases.

How Does Asbestos Exposure Develop Into Deadly Mesothelioma?

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It is a proven fact that asbestos exposure can develop into deadly mesothelioma. But how does this happen to healthy cells? Microscopic asbestos fibers are inhaled into the lungs, yet the deadly mesothelioma disease can appear in physically remote mesothelial cells¹.

Latest experiments

Arti Shukla, Ph.D., associate professor of pathology and laboratory medicine at the University of Vermont’s Larner College of Medicine and a UVM Cancer Center member, along with colleagues, used two groups of cells – lung epithelial cells¹ and macrophages¹ – in their study because these two cell groups are the first that asbestos fibers encounter when inhaled. These cells were divided into two groups: one exposed to asbestos fibers and the other left alone to grow normally. They grew for three days.

At that time, they collected the exosomes² released by the cells. By examining the proteins in the exosomes, they found the group exposed to asbestos had a great deal of suspicious proteins as opposed to the non-exposed group. The exosomes containing the suspicious proteins were then added to healthy mesothelial cells. After four days, they found significant changes to many cancer-related genes in the previously healthy mesothelial cells.

Why is this important?

This study suggests that exosomes, with their ability for intercellular communication, can alter cellular genetics – even from a distance. It also indicates these exosomes and their proteins, can act as biomarkers pointing to the development, or even the progression, of asbestos-related disease.

Shukla states, “Our findings suggest that cells in one region of the body are capable of sending messages to cells in a distant location, and can cause significant genetic changes. This communication from injured or diseased cells to healthy cells has the potential to initiate changes that might lead to cancer or other diseases.”

Editor-in-chief of The FASEB Journal, Thoru Pederson, Ph.D., adds, “These intriguing findings go a good ways toward explaining the conundrum of how a pulmonary irritant triggers distant effects. They also add to the burgeoning array of studies that link exosome-based communication to pathogenic events.”

In summary, this is an important step toward treating – and  perhaps one day curing – mesothelioma.

Vocabulary of the disease

¹Cell types involved:

Mesothelial cells: These cells form a slippery, non-adhesive protective layer, the mesothelium, in the body’s serous cavities and internal organs.

Epithelial cells: These are the body’s safety shield. Your skin is comprised of millions of these cells, but they also line all your organs, intestines, blood vessels, and throat.

Macrophages: This is a type of white blood cell, carried by your blood to the site of infections. When epithelial cells are damaged, they release chemicals to attract macrophages. They can clean up harmful bacteria, viruses, and dead cells.

²Exosomes: These are very small vesicles that carry RNA and proteins. They were once thought of as merely garbage cans for cell debris, but now are the focus a great deal of scientific interest. Researchers found they enable intercellular communication that may lead to minimally invasive diagnostics.

Potential New Treatment for Mesothelioma

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In a study by researchers led by Dr. Antonio Giordano at the Sbarro Institute for Cancer Research and Molecular Medicine at Temple University and his colleagues at the University of Siena, Italy, a potential new treatment for mesothelioma appears promising.

This treatment involves repurposing a drug already approved for the treatment of pinworm parasite infections. Since this drug is already approved for one use, getting approval for another use will be less expensive, and even more importantly, can be brought to patient use more quickly than with a new drug. Because mesothelioma, almost always connected to asbestos exposure, is a deadly cancer with no current effective treatment, researchers throughout the world creatively investigate possible methods to stop – and soon cure – this deadly disease.

This anti-parasitic drug is named pyrvinium pamoate. It was found to alter the downstream genes in the WNT signaling pathway – pathways consisting of proteins that pass signals into a cell through cell surface receptors. These genes in the signaling pathway may be the cause of the aggressiveness of mesothelioma and its resistance to conventional therapy.

According to Dr. Giordano, whose study was published in the Journal of Cell Physiology, “The results of this study represent a step forward in the development of new treatments for patients with mesothelioma. Pyrvinium pamoate is able to affect important features of mesothelioma aggressiveness, suggesting that the repurposing of this drug for mesothelioma treatment could represent a new promising therapeutic approach.”

Author of the study, Marcella Barbarino of the University of Siena stated, “These are encouraging results, especially considering that drug repositioning, using already approved drugs for new indications, is a promising strategy to identify active molecules for a more rapid and less expensive clinical translation compared to de novo drug development.”

Sbarro Health Research Organization (SHRO) and the Mesothelioma Applied Research Foundation funded this study, dedicated to Mr. Vittorio Stortino in his memory.

We are grateful for the work being done to urgently find a cure for this deadly disease and for the hope it gives to all those affected.