Author: Lisa Hyde-Barrett
Could Dying Mesothelioma Cells Make The Surviving Cells Fight Harder to Stay Alive?
The goal of treatments, such as chemotherapy and radiation, is to kill off mesothelioma cells to increase the survival for the patients. But researchers report they discovered dying cancer cells communicate to their surviving cells that can then alter their genetic makeup to fight back the drugs. Finding a way to block this cell-to-cell communication is now the target for development of a novel cancer treatment.
Researchers from The University of Alabama at Birmingham, Russia and South Korea looked closer at the status of cells in glioblastoma tumors to determine the relationship dying cells have with their neighboring active cancer cells. They found that cells undergoing apoptosis, or are dying, send signals to adjacent tumor cells that encourages them to become more aggressive and resist treatment, according to a June 21 press release from UAB announcing the findings.
Dying Cells Send Signals to Counterparts
The team used mouse models injected with a combination of apoptotic and “healthy” glioblastoma cells. When viewed in brain scans, the combination showed “much more aggressive tumor growth” and were “more therapy-resistant” than either the “healthy” cancer cells or the dying cells alone.
The researchers determined the dying cells secrete apoptotic extracellular vesicles (apoEVs) that can alter the RNA of the recipient cells which promotes drug resistance and “aggressive migration” of the cancer cells.
“This mechanism thus becomes a possible target for new therapies to treat glioblastoma, a primary brain cancer, and the mechanism may apply to other cancer types as well,” the researchers determined.
Mesothelioma is a rare, aggressive cancer that leaves oncologists and patients with few treatment options. Typically the patients are treated with chemotherapy, that works temporarily, but the insidious cancer often develops a resistance to the therapy rendering it ineffective.
“Clinically, our data may provide the rationale to the molecular targeting of RNA splicing events or specific splicing factors for novel cancer therapies,” said Ichiro Nakano, M.D., Ph.D., academic neurosurgeon at the University of Alabama at Birmingham and leader of the international study. “This may lead to decreased acquisition of therapy resistance, as well as reduction in the migration of cancer cells.”
Although the researchers did not look at mesothelioma cell apoptosis, research into other aggressive, difficult-to-treat cancers can lead to insight into the asbestos-caused cancer. Nearly 3,000 Americans are diagnosed with some form of mesothelioma each year. Survival is often less than one year.
Read the full study in the June 21 issue of Cancer Cell.
Sources:
- June 21 issue of Cancer Cell
https://www.cell.com/cancer-cell/fulltext/S1535-6108(18)30226-5 - The University of Alabama at Birmingham
http://www.uab.edu/news/research/item/9543-dying-cancer-cells-make-remaining-glioblastoma-cells-more-aggressive-and-therapy-resistant
Mesothelioma Nurse Discusses Suicide Prevention Resources
Recently, two very public figures, who looked like they had it all, committed suicide. Those closest to them revealed that they had struggled with their demons for many years. When someone is a celebrity we think we “know” them: we know their work, but we do not know them.
This is a wake-up call for all of us to be more aware of how we and our loved ones are really feeling. Suicide happens because the person wants their overwhelming ‘pain’ to end. According to research, 90% of people who die by suicide have an existing mental illness or substance abuse problem at the time of their death.
Depression and depressive illness are mood disorders of the brain. It is caused by a chemical imbalance in the brain, a disruption of the brain’s balance. The two chemicals that are thought to be imbalanced are serotonin and norepinephrine. It is not a weakness, or a character problem. The important thing to note is that depression can be successfully treated.
The number of people who seek treatment for an episode of major depression in the U.S. is only 50% of the total that suffer from depression. According to the National Alliance of Mental Health, 80% to 90% of people who seek treatment for depression are treated successfully using therapy and/or medication.
People diagnosed with cancer have a nearly two-times a higher suicide rate than the general population. Being diagnosed with malignant mesothelioma is a life-altering event. There are treatment options, but the options need to include the whole person. Everyone needs to know that when things are looking hopeless or they are in unbearable physical or emotional pain there is help. The feelings are real, but there are treatments that work.
Not to be forgotten, are the families of patients who are being treated for mesothelioma and those who have lost loved ones from mesothelioma. For them, the pain of the loss coupled with other existing issues might make suicide seem like the only option to stop their pain. It is vital for all to realize there is help available and the help does work!
RESOURCES:
www.Save.org – Suicide Awareness Voices of Education
National Suicide Prevention Lifeline: 1-800-273-8255
Local Emergency Rooms can also help find you help.
The Potential of Nanoparticles in Treatment of Mesothelioma Patients
In May, Mesothelioma Help reported that researchers from the University of North Carolina Lineberger Comprehensive Cancer Center found a “promising new nanotechnology-based delivery method” for immunotherapy using nanoparticles. Now, another team of researchers report they have found a way to use this microscopic drug delivery system “for diagnostics, therapy, or both” for cancer care.
In the latest research from the Moscow Institute of Physics and Technology (MIPT), a team of biophysicists report they engineered a way to cover nanoparticles with biological molecules that allows them to deliver therapy and then examine the effect the drug has on the cancer cells. The particles, for example, can carry properties that can home in on the cancer cells to pinpoint the therapy as well as fluorescent properties to light up the cancer cells for diagnostics.
Using theranostics, the integration of therapeutics and diagnostics, in mesothelioma care is an exciting prospect. Most of the treatments used for mesothelioma, a terminal asbestos-caused cancer, eventually become ineffective, but it may not be discovered until the mesothelioma cancer is no longer treatable. With diagnostic capabilities embedded in the nanoparticles, the effectiveness of the treatment can be monitored as needed.
The researchers developed a “molecular glue” using the barnase-barstar protein pair to hold the therapeutic and diagnostic components together. The success of this research is due to this glue that can bind up to one million times greater than other types, and can bind with antibodies, drugs, fluorescent molecules and targeting agents. When the two proteins are tightly bound they form “a bifunctional compound” with both therapeutic and diagnostic properties, that enables targeted drug delivery.
This type of personalized medicine follows the concept that the cancer’s genetic makeup can be used to tailor a patient’s treatment. Mesothelioma can grow at a different rate and respond to different treatments in each patient, that is why mesothelioma patients need treatment that is aimed at their unique characteristics. By allowing the therapeutic aspect of the nanoparticles to be modified, this personalized care optimizes the potential for success of the treatment.
“The demonstrated capabilities show this method to be a promising alternative to commonly used … techniques in nanobiotechnology, theranostics, and clinical applications,” wrote the authors in the study published in ACS Applied Materials & Interfaces.
Mesothelioma, a rare form of cancer typically affecting the lining of the lungs, is highly aggressive and is resistant to many cancer treatments making it a difficult disease to treat effectively. The prognosis for mesothelioma patients is usually grim: the average survival time varies from 4 – 18 months after diagnosis. Approximately 3,000 Americans are diagnosed with mesothelioma each year.
The paper was published in the April 27 issue of the journal ACS Applied Materials & Interfaces.
Two-Drug Combination Found Effective in Lung Cancer May Increase Survival in Mesothelioma Patients
It has been over two years since Mesothelioma Help reported on the start of a clinical trial that used a combination of immunotherapy drugs to treat lung cancer. The trial was designed to determine whether the two drugs would work better than one in the treatment of cancer patients. Now, researchers say early results of the trial show the pair of drugs are “surprisingly effective” at controlling the progression of lung cancer.
Immunologist John Wrangle, M.D. and his colleague Mark Rubinstein, Ph.D., both from the Hollins Cancer Center at The Medical College of South Carolina (MUSC), are so excited with the results that they are “flirting with the idea” of using the word “cure” on some of the non-small cell lung cancer patients treated with the novel therapy, according to an April 5 press release.
“People don’t talk about ‘curing’ patients with metastatic lung cancer,” said Wrangle. “We now get to flirt with the idea for certain patients using immunotherapy. And at the very least we have a significant proportion of patients enjoying prolonged survival even if we can’t call them ‘cured’.”
The researchers report that nearly every lung cancer patient will relapse after chemotherapy, and with the advent of immunotherapy, some of them will turn to it as their next mode of treatment. But still, they say, less than 20 percent of NSCLC patients will respond to immunotherapy, and it too will eventually stop working. Pleural mesothelioma is an equally stubborn cancer and treatment for the asbestos-caused cancer is very similar to NSCLC treatments. Mesothelioma patients are anxious to find a new treatment that will increase their survival beyond the typical prognosis of less than one year.
Hoping to break that poor response record, the two researchers turned to nivolumab (Opdivo), an FDA-approved immunotherapy, and ALT-803, an experimental immuno-oncology treatment. In the initial test of 21 patients, nine previously had either become resistant to their previous treatment or had stable disease at the time of the trial. Looking specifically at those nine patients, the researchers report that “100 percent either had stable disease or had a partial response to the treatment used in this study.”
Opdivo, developed by Bristol-Myers Squibb, works by blocking the PD-L1 protein and activating the immune system, leading it to attack and kill cancer cells. ALT-803, being developed by Altor BioScience Corporation, is an immune stimulation drug.
“There are very few people in human history who get the privilege of developing a new therapy for any human disease, much less cancer,” said Wrangle. “That’s such an amazing privilege to be able to do that.”
The two admit there is still a long way to go “before the new combination of drugs can be used outside of a clinical trial.” They hope to treat hundreds of patients in a trial to better understand the proper mix of the drugs.
Ongoing research into lung cancer, mesothelioma and other aggressive cancers is vital to continue to break ground in treatments previously not considered. Mesothelioma patients should continue to work with their medical team to assess how they can participate in this critical research.
Read more about the study in the April 4 issue of The Lancet Oncology.
https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30148-7/fulltext
For more information about the trial see ClinicalTrials.gov.
https://clinicaltrials.gov/ct2/show/NCT02523469
“Lung Decision Precision” Screening Tool May Lead to Early Detection of Mesothelioma
The key to increased life expectancy when battling lung cancer, and other extremely aggressive cancers such as mesothelioma, is early detection. Unfortunately, while there are standard screening tests and guidelines for breast cancer, colon, and prostate cancer, lung cancer screening tests are limited to high risk patients, defined as life-long heavy smokers. Now, researchers have developed a personalized lung cancer screening decision tool which incorporates past asbestos exposure as a criteria to guide individuals and physicians in determining their lung cancer screening options.
Researchers from the University of Michigan have unveiled a lung cancer screening Q&A tool that can be used by medical professionals to identify people who may benefit from a low-dose computed tomography (LDCT) screening. For people who do not have any symptoms often associated with lung cancer or pleural mesothelioma, such as difficulty breathing, coughing or fatigue, there is seemingly no reason to screen for lung cancer.
That is why the personalized Lung Decision Precision tool for physicians, which presents a series of questions targeting the person’s smoking history and asbestos exposure, is important. The tool is designed to open discussion between the physician and patient to determine whether a lung screening is appropriate.
“This allows us to identify which patients are in the preference-sensitive zone for the decision about screening, and which ones have a very clear potential benefit to them,” said Tanner Caverly, M.D., M.P.H., an assistant professor in the Division of General Medicine and Department of Learning Health Sciences at the U-M Medical School.
The Lung Decision Precision Tool asks the critical question: “Has the patient been exposed to asbestos at work?” Based on a “yes” answer, the patient is asked to confirm the following:
- You worked in one or more of the following occupations: asbestos worker, insulator, lagger, plasterboard worker, dry waller, plasterer, ship scaler, ship fitter, rigger, shipyard boilermaker, shipyard welder, shipyard machinist, shipyard coppersmith, shipyard electrician, plumber/pipefitter, steamfitter, or sheet metal worker.
- You worked in this job for at least 5 years.
- You began working in this job at least 15 years ago.
Asbestos is a human carcinogen, known to cause lung cancer and pleural mesothelioma, a cancer of the lining of the lungs diagnosed in nearly 3,000 Americans each year. The U.S. Environmental Protection Agency warns that there is no safe level of exposure. In addition, the Occupational Safety and Health Administration reports, “every occupational exposure to asbestos contributes to the risk of getting an asbestos related disease.”
While no longer used in new buildings in the U.S., asbestos was added to a variety of products including insulation, steam pipes, furnace ducts, floor tiles and roofing shingles, in buildings and homes built prior to EPA regulations were put in place in the 1970’s. People who worked in construction, ship-building, plumbing and in the military are at a higher risk than others of developing mesothelioma.
The only recommended screening test for lung cancer is LDCT, according to the Centers for Disease Control and Prevention. During an LDCT an X-ray machine scans the body and uses low doses of radiation to make detailed pictures of the lungs to help find abnormal areas that may be cancer. The American Cancer Society reports that in a study of 50,000 smokers or former smokers aged 55 to 74 researchers found that people who got LDCT had a 20% lower chance of dying from lung cancer than those who got chest x-rays.
Mesothelioma is often not diagnosed until symptoms are present, and the cancer is in its late stages. At this point, prognosis is often less than one-year. Stopping tumor growth and preventing metastasis is especially critical for mesothelioma and lung cancer where the diseases are highly aggressive. This can only be achieved if the mesothelioma cancer is detected early.
“As a clinician I’d like to have this [tool] for many of the things I do, where it would be meaningful to know how beneficial something could be for the individual patient, and we could talk about whether it’s indicated for them,” said Caverly.
The research team also launched a companion website, “Should I get screened”, for patients that includes easy-to-understand information about the pros and cons of lung cancer screening, and includes a “lung cancer risk calculator.”
If you have been exposed to asbestos in the past, talk to your doctor about the Lung Decision Precision tool.
Find out more about the tool in the May 29 issue of Annals of Internal Medicine.
Sources:
- University of Michigan
http://ihpi.umich.edu/news/scan-or-not-scan-research-shows-how-personalize-lung-cancer-screening-decisions - Annals of Internal Medicine
http://annals.org/aim/article-abstract/2682684/identifying-patients-whom-lung-cancer-screening-preference-sensitive-microsimulation-study - Lung Decision Precision tool
https://share.lungdecisionprecision.com/ - Should I get screened
http://www.shouldiscreen.com/ - The American Cancer Society
https://www.cancer.org/cancer/lung-cancer/prevention-and-early-detection/early-detection.html - Occupational Safety and Health Administration
https://www.osha.gov/SLTC/asbestos/
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