NIH “All of Us” Program May Guide Research for New Treatments For Mesothelioma

The National Institutes of Health has announced its “All of Us” research program is now open for enrollment. The program is looking for one million people to share their health information over decades to be used to speed up health research breakthroughs and to advance precision medicine.

Part of the Precision Medicine Initiative introduced by President Obama in January 2015, the “All of Us” program was created to support research to develop more effective ways to prolong health and treat disease. With the data bringing so many different “genes, microbiomes, environments, and lifestyles,” the information will make possible “more effective, targeted treatments for diseases like cancer and diabetes.”

“Imagine the power of a project that asks 1 million people from across the United States to volunteer to help find answers about virtually all health conditions we face,” said Alex M. Azar II, the secretary of Health and Human Services, and Francis S. Collins, the director of the National Institutes of Health, in an opinion piece they wrote in USA Today on May 7.

https://www.usatoday.com/story/opinion/2018/05/07/all-us-research-medical-issues-national-institutes-health-column/584949002/

Data Opens Door to Precision Medicine

The ultimate goal of the project is to create a database containing genetic information, biological samples, and dietary and lifestyle information of one million Americans who volunteer to share this information and, potentially, their electronic health records. This information will be used to “lay scientific foundation for precision medicine for many diseases,” according to the NIH.

https://syndication.nih.gov/multimedia/pmi/infographics/pmi-infographic.pdf

Precision, or personalized, medicine targets health care to the unique makeup of people and their diseases optimizing the potential for success of the treatment. This approach is especially beneficial for mesothelioma and other rare disease research.

Hoping for enrollees from “communities that have inadequately benefited from previous findings and breakthroughs,” Collins and Azar see the data as a way to “help science answer important questions about today’s growing epidemics and mysteries.” Mesothelioma continues to confound researchers and oncologists, so the unprecedented amount of data can only help improve outcomes.

“All of Us” Is Important to Mesothelioma Treatment

“By signing up for All of Us, you will join a mission to accelerate an emerging field called precision medicine,” said Azar.

Nearly 3,000 Americans are diagnosed with mesothelioma each year. There is no cure for the cancer, but treatments intended to go after the unique characteristics of the disease have shown promise. Oncologists and mesothelioma patients are hopeful that this approach to research will bring personalized care to the forefront of treatment strategies.

The NIH reports 27,000 people have already enrolled in the study.

“We have the opportunity to better understand and anticipate how the complex interactions of behavioral, biological, environmental and socioeconomic factors may affect the health of each us — as individuals,” said Azar and Collins.

“Understanding these interactions may be key to developing treatments that deliver more value and better health for every American.”

For more information and to enroll, visit JoinAllofUs.org.

Is Mesothelioma Treatment Without Side Effects Possible?

Chemotherapy is vital in the treatment of mesothelioma. However, it often results in side effects, such as low blood cell counts, thinned or brittle hair, loss of appetite or weight, diarrhea, nausea and vomiting, that can be difficult for patients to manage and can sometimes outweigh the benefits of the treatment. Now, researchers report they have developed a technique for delivering medications that are “free of side effects.”

Researchers from the University of Virginia School of Medicine report that drugs are designed to target an offending molecule, that which makes a person sick, by completely blocking its access to a cell. By doing so, however, any good that the molecule may offer is also stifled. The team, led by J. Julius Zhu, professor of pharmacology at UVA, determined that molecules have different functions throughout a cell, and they were able to develop a targeted delivery method for drugs that can home in on a specific location of a cell while avoiding those locations that could lead to side effects, according to a July 5 press release from the University.

“The problem with side effects is caused because you just could not distinguish the molecules doing different things in the same cell,” Zhu said. “If you blocked a molecule, you blocked it regardless of what it was doing. And that usually has unwanted side effects.”

Treatment for mesothelioma, a rare, aggressive form of cancer caused by exposure to airborne asbestos fibers is complex and, depending on the stage of the disease, typically involves a multi-modal approach including surgery, radiation and chemotherapy. While these treatment options are among the keys to improve the chances of the battling the disease, they can come with pain and sometimes debilitating side effects leading to a poor quality of life. Patients often need to discontinue their mesothelioma treatments that are killing off the cancer cells because the side effects are nearly worse than the disease.

According to Zhu, the concept behind this targeted approach was “simple,” but the execution of it took many years. The new drugs, he says, will be especially useful for cancers, and “adds a new level of precision to the concept of precision medicine – medicine tailored exactly to a patient’s needs.” Precision medicine has the best chance of helping a mesothelioma patient achieve extended survival.

The technique will also speed up the development of new treatments by letting researchers more quickly understand what molecules are doing and which should be targeted, according to the press release.

Finding a way to safely deliver toxic chemotherapy and other anti-cancer drugs to mesothelioma patients is critically important to allow patients to continue to receive treatments without having other aspects of their health compromised from dangerous side effects.

Nearly 3,000 Americans are diagnosed with mesothelioma each year.

Read the full study in the May 16 issue of the journal Neuron.

https://www.cell.com/neuron/fulltext/S0896-6273(18)30283-6

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

Keytruda and Mesothelioma Explained | Mesothelioma 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

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