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New Immunotherapy Drugs Show Promising Results for Certain Cancers in Clinical Trials. Is Mesothelioma Next?

Participation in Clinical Trials is how progress is made in medical research.  The trials are regulated and must conform to rigorous standards and be able to be replicated. Research scientists dedicate their careers to making progress with treatments for diseases using Clinical Trials. The inclusion and exclusion criteria are very specific. Some Clinical Trials are not able to be done due to lack of enrollment. Participation is voluntary and only with informed consent that the patient can withdraw at any time. In the United States it is estimated that only 5% of adults eligible to participate in a Clinical Trial sign on.

Progress can be slow and results are often not what the researchers had hoped for. Responses can vary by individual participants and success is often made in small percentages of people responding to the treatment. 

This past week some very exciting news was published in the New England Journal of Medicine and reported widely in the media.  A surprising report was published of the results of a Clinical Trial with a small sample of patients diagnosed with a specific mismatch-repair deficiency rectal cancer and the immunotherapy drug Dostarlimab, brand name Jemperfi. This specific type of rectal cancer makes up 5-10% of all rectal cancers. 

Before beginning the standard treatment for this type of rectal cancer, which is chemotherapy followed by radiation followed by surgery, these patients joined a Clinical Trial testing Dostarlimab infusions before the standard treatment.  Dostarlimab is classified as an immunotherapy drug.  It has been approved by the FDA for treatment of certain types of endometrial cancers. The results were a surprising 14 out of 14 patients having a full remission.  No evidence of their disease was found!  For 100% of the patients enrolled in the study to have no evidence of disease after six months of treatment is what researchers dream of.  The importance of this response is exciting for all of the patients and researchers and for possible results with other cancers. More research with a larger number of patients will need to be done.

These results  are encouraging for research for malignant mesothelioma that are ongoing with some Clinical Trials including immunotherapy drugs. 

With renewed enthusiasm we encourage those diagnosed with Malignant Mesothelioma or any other cancer to checkout www.ClinicalTrial.gov or ask your treatment team about eligibility to participate in a Clinical Trial. 


Blood Test - Mesothelioma Survival

Breakthrough Blood Test May Extend Mesothelioma Survival

Just last week, MesotheliomaHelp reported on a corporate partnership for blood test tools that will bring improved results in the detection of key lung cancer mutations. Blood biopsies are shown to be fast and accurate, as well as less stressful on the patients. Now, in another breakthrough using liquid biopsies, researchers report success in the early detection of mesothelioma and screening for multiple cancers using one tool.

Researchers from Johns Hopkins University have developed the CancerSeek blood test that is able to screen for eight different types of cancers and can help pinpoint the location of the tumor. In a recent study of 1,005 cancer patients, the results had a “greater than 99 percent specificity for cancer,” according to a Jan. 19 press release from Johns Hopkins University.

[expert_info author=”Bert Vogelstein, Johns Hopkins University”]”This test represents the next step in changing the focus of cancer research from late-stage disease to early disease, which I believe will be critical to reducing cancer deaths in the long term.”[/expert_info]

Although there are screening options for some cancers, such as breast and prostate,  mesothelioma, and many other cancers, are diagnosed after the patient goes to a doctor exhibiting some of the signature symptoms of cancer: unexplained weight loss, extreme fatigue and a persistent cough. CancerSeek results had a sensitivity ranging from 69 percent to 98 percent in five cancers that do not currently have any screening test availables, including ovarian, pancreatic, and esophageal cancers.

The test, according to the researchers, looks at eight common cancer proteins and the presence of cancer gene mutations from DNA circulating in the blood. The team developed a “small yet robust panel” that could detect at least one mutation and not lead to false-positives. The test is used for cancer detection only, and does not detect specific biomarkers to drive treatment.

“The use of a combination of selected biomarkers for early detection has the potential to change the way we screen for cancer…,” says Nickolas Papadopoulos, senior author and professor of oncology and pathology at Johns Hopkins.

Pleural mesothelioma, a deadly cancer of the lungs caused by past exposure to asbestos, has a long incubation period where patients may not exhibit symptoms for decades after exposure. By then the disease is already at an advanced, incurable stage.

Early detection of cancer through screening reduces mortality from many cancers, including lung and colon, according to the National Cancer Society. When treating mesothelioma patients, the best outcome is achieved with early detection of the disease by increasing treatment options and improving the patients’ quality of life while battling the cancer.

The  tests are still in the early stages of research and are not yet available; however, they may be helpful in diagnosing mesothelioma in the future. In fact, the team anticipates a relatively inexpensive test that may be conducted by a primary care provider.

Read the results of the study in the Jan. 18 issue of the journal Science.





Man Behind Mesothelioma Warrior Ray Nye Caring for His Wife

Turning Off Certain Enzymes Could Stop Mesothelioma Growth

Researchers realize that one of the best ways to fight cancer is to stop it from growing and metastasizing in the first place. However, finding the right way to do that is not easy. Now, researchers believe that by turning off certain enzymes they can stop cancer cells from dividing. This discovery may stop cancer in its tracks, and bring new treatments that could extend the lives of mesothelioma patients.

Researchers from Uppsala University, Karolinska Institutet, and the University of Oxford, began to look deeper into finding a way to switch off enzymes as a promising strategy to fight cancer. Tailored drugs are needed to shut down an individual enzyme, but before they could look at new therapies, they needed to better understand how cancer-fighting drugs get to their targets.

The team of scientists turned their focus deep into the cells to a cell membrane protein dehydroorotate dehydrogenase (DHODH), a key anticancer target known to play a role in cell proliferation, according to a Jan. 19 press release from Uppsala University. They conducted a series of tests to determine how lipids, or building blocks of the cell membrane, and drugs bind to the DHODH enzyme. By better understanding this mechanism, they can better understand how to drive drugs directly to the disease.

“To our surprise, we saw that one drug seemed to bind better to the enzyme when lipid-like molecules were present,” says assistant professor Michael Landreh, Karolinska Institutet. In addition, they found that a lipid present in the mitochondrial respiratory chain complex, or the cell’s energy source, binds to the enzyme. The researchers concluded that DHODH may “use special lipids to find its correct place on the membrane.”

Research suggests that tumor metastases are responsible for approximately 90% of all cancer-related deaths. Funding research to find ways to have drugs home in directly on the disease brings hope to every cancer patient. In the case of mesothelioma, an incurable, asbestos-caused cancer, that quickly spreads to other organs leaving patients with few treatment options, halting cancer growth could lead to extended survival. Survival is typically about one year.

“By studying the native structures and mechanisms for cancer targets, it may become possible to exploit their most distinct features to design new, more selective therapeutics,” says Sir David Lane, Karolinska Institutet.

To find out more about this research, read the full study in the Jan. 18 issue of Cell Chemical Biology.


Lung Cancer Awareness Month - Mesothelioma

Researchers Seek to Understand Why Lungs Are Susceptible To Cancer

The body has a cadre of defense mechanisms that work together to fight off illness and diseases. When they fail, however, a person can be left fighting a deadly disease like mesothelioma. Now, researchers believe that the same defense meant to prevent people from having a reaction to breathing in daily environmental exposures could be the same mechanism that allows cancer cells to spread and grow in the lungs.

According to an Aug. 25 press release from the Ohio State University Comprehensive Cancer Center, researchers report that the oxygen breathed in can suppress immune responses to cancer. They found that oxygen-sensing proteins, or PHD cells, limit inflammation by T-cells, the cells in the immune system that kill bacteria and cancer. In the “highly oxygenated lung microenvironment” the PHDs limit the T-cell functions, thus, setting the lung up as a “fertile ground for metastasis.”

“The same ‘normal’ mechanisms put in place to suppress immune responses against harmless material taken into the body during the act of breathing can also suppress immune responses to the colonizing cancer cells that lead to metastatic tumors in the lungs,” said David Clever, PhD, first author of the manuscript and a current medical student at Ohio State. “This creates an immunologically favorable niche – meaning the environment is prime for cancer cells to slip through the immune system’s defenses, thrive and grow in the lungs.”

The American Cancer Society reports that it is cancer metastasis, and not the original cancer diagnosis itself, that is the cause of nearly all cancer deaths. In fact, 90 percent of all cancer deaths are due to metastasis. Lung cancer and mesothelioma can spread to other organs of the body, including spreading to the other lung.

Mesothelioma, an unusual form of cancer caused by breathing in asbestos fibers, can take decades to show symptoms. Mesothelioma treatment follows a similar treatment protocol to lung cancer, so each new discovery related to lung cancer brings hope to the patient community.

The Ohio State team found that by blocking the PHD proteins, they could enhance T-cell responses against cancer and limit metastasis to the lung. Through testing the theory in mice using adoptive cell transfer immunotherapy, or manipulation and re-injection of T-cells, the researchers were hopeful their findings could lead to new therapies.

“Although our finding is in mice, we are eager to test whether disruption of the oxygen sensing machinery in T cells — with drugs, genetics, or regulation of environmental oxygen — will enhance the efficacy of T-cell mediated immune therapies for cancer in humans.”

2,500 to 3,000 people are diagnosed with mesothelioma each year in the U.S. There is no cure for the cancer, however, immunotherapy treatments, available to limited patients, have shown success in extending survival in mesothelioma patients.

The study can be found in the Aug. 25 issue of the journal Cell.

Know more about Mesothelioma and how you can deal with it.

Role of Mesothelin in Mesothelioma

Mesothelin May Play Multiple Roles in Spread of Mesothelioma, Other Cancers

Mesothelin is a protein found on the surface of some cells in the human body. Its biological purpose is a bit of a mystery frankly. But it occurs in overabundance in certain types of cancer cells including ovarian cancer, pancreatic cancer and mesothelioma, a cancer of the lining of the lungs and abdomen. Therefore, it’s on scientists’ radar screen.

Scientists are evaluating the role of mesothelin in the spread of cancer and its potential usefulness as a signal of cancer for doctors who are trying to diagnose a patient’s disease such as mesothelioma, a cancer caused by asbestos exposure. There are treatments for mesothelioma, but as yet, there is no known cure. Approximately 2,500 to 3,000 people in the U.S. are diagnosed with malignant mesothelioma each year in the U.S., primarily as a result of asbestos exposure at a workplace or during military service.

In a mesothelioma researcharticle published in February 2013 in the journal Anti-Cancer Agents in Medicinal Chemistry, medical researchers at the National Cancer Institute in Bethesda, Maryland and East China Normal University in Shanghai, say that there are  three ways that mesothelin may play a role in the advance of cancer, as previous studies have suggested:

  • Implantation — Mesothelin may aid in the implantation of tumors in the abdominal cavity, leading to peritoneal mesothelioma;
  • Survival — Mesothelin may play an important role in the survival of cancer cells;
  • Resistance — The presence of mesothelin may cause resistance to certain chemotherapy drugs.

As a result of the key role of mesothelin, the researchers say that a drug that neutralizes the functionality of mesothelin may be helpful in cancer treatment, making chemotherapy drugs more effective, for instance. Some antibody drugs that disrupt the function of mesothelin are currently being evaluated in clinical studies.

The researchers say additional research is needed to evaluate the role of mesothelin in the growth and spread of malignant tumors, cancer cell survival and drug resistance. They conclude that studies on mesothelin biology may give opportunities for more effective antibody therapy targeting mesothelin in solid tumors.

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