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.

Combination of Electric Fields and Chemotherapy May Be A New Treatment Option for Pleural Mesothelioma Patients

The key to increasing survival for mesothelioma patients is to kill the cancer cells before they can spread to other organs. Treatment options, including surgery, chemotherapy and radiation, all contribute to a patient’s survival, but many times the prognosis remains unchanged. Now, one company has turned to experimenting with delivering electromagnetic waves to the chest of pleural mesothelioma patients and reports improvements in overall survival when combined with chemotherapy.

Novocure, a UK-based medical device company that develops and markets Tumor Treating Fields delivery systems, developed the novel devices as an alternative way to destroy tumor cells while sparing healthy tissue. Already approved by the U.S. Food and Drug Administration for the treatment of brain cancer, the device is now in a Phase II clinical trial for pleural mesothelioma patients.

In April, researchers gave an interim review of the STELLAR clinical trial reporting that the first 42 pleural mesothelioma patients treated with the combination of Tumor Treating Fields (TTF) and pemetrexed and cisplatin or carboplatin had a one-year survival rate of 80 percent, compared to 50 percent in the chemotherapy only patients. Median progression free survival was 7.3 months versus just 5.7 months in the chemotherapy controlled group.

“We are extremely pleased with these top-line results, which bring us one step closer to realizing the potential for a new treatment for mesothelioma patients in desperate need,” said Dr. Eilon Kirson, Novocure’s Chief Science Officer and Head of Research and Development, in an April 17 press release.

The NovoTTF-100L device used in the clinical trial provides mesothelioma patients with a round-the-clock treatment option that allows them to maintain an active lifestyle without interference to activities such as walking outdoors, shopping, and cleaning. Connected to the patient via insulated electrode arrays placed on the upper torso, the device delivers low-intensity alternating electric fields to the region near the mesothelioma tumors. The TTF is inconspicuous and light enough to carry to most functions and activities. The device needs to be active approximately 18 hours a day. According to the company’s website there are no limiting side effects.

“Mesothelioma is the first torso indication for which Novocure will pursue FDA approval,” said Dr. Kirson.

Novocure previously received a Humanitarian Use Device (HUD) designation for the use of TTF for pleural mesothelioma. The next step is to submit a Humanitarian Device Exemption (HDE) application to the FDA. For medical devices, an HDE exempts the businesses from proving effectiveness of the device. However, the company must show that the HUD “will not expose patients to an unreasonable or significant risk of illness or injury and the probable benefit to health from use of the device outweighs the risk of injury or illness from its use, ” according to the HDE application requirements.

Pleural mesothelioma, a rare form of cancer affecting the lining of the lungs, is highly aggressive and is resistant to many cancer treatments. Most often diagnoses are not made until symptoms appear and the disease has progressed to an advanced stage leaving the patient with life-threatening complications. 3,000 Americans are diagnosed with mesothelioma each year.

Sources :

STELLAR clinical trial
https://clinicaltrials.gov/ct2/show/NCT02397928
Novocure’s Chief Science Officer and Head of Research and Development
https://www.novocure.com/novocure-reports-positive-top-line-results-from-stellar-phase-2-pilot-trial-in-mesothelioma/
NovoTTF-100L
https://www.novocuretrial.com/stellar-mesothelioma/living-with-ttfields/
Humanitarian Device Exemption
https://www.fda.gov/medicaldevices/deviceregulationandguidance/howtomarketyourdevice/premarketsubmissions/humanitariandeviceexemption/default.htm
HDE application requirements
https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/PremarketSubmissions/HumanitarianDeviceExemption/ucm563286.htm

Protein Identified As Target to Halt Spread of Mesothelioma and Other Cancers

Time and again mesothelioma patients discover that while their cancer treatment initially appeared effective, cancer cells slipped away and spread to other areas of their body. It is this metastasis that eludes scientists. Now, researchers report they have identified a protein they can target that will prevent the spread of cancer cells.

The LTBP3 protein, known to fuel blood vessel growth, in effect, spurs cancer cells to spread beyond the initial tumor site by traveling in these new “highways” through the body, according to a Feb. 16 press release from the Scripps Research Institute. Patients who had lower levels of this protein had a better prognosis, leading the researchers to focus on finding a way to target LTBP3.

The research team looked more closely at LTBP3 and TGFβ, a molecule that has been linked to both growth and suppression of cancer. They knew the two “partner” to regulate TGFβ, but they wanted to find if the two worked in concert to spread cancer. However, because TGFβ is both good and bad, they had to find a way to suppress the molecule’s harmful effects, without interfering with the benefits for slowing cancer growth.

Using chick embryo and mouse models, they suppressed LTBP3 and discovered that without it, primary tumor cells could not metastasize efficiently. This indicated that LTBP3 is involved very early in the metastasis process. The team concluded “LTBP3 levels can indicate better overall survival” in some cancer patients.

The team reports that LTBP3 is a good “upstream” drug target for early stage tumors without affecting the role of TGFβ. Their next step is to determine how LTBP3 and TGFβ partner in the induction of new blood vessels deep within a tumor.

Finding a way to halt the spread of deadly cancer cells is critical for improving survival in mesothelioma patients. In fact, according to the American Cancer Society, “With upwards of 90% of all cancer suffering and death associated with metastasis, it is the single most significant challenge to management of the disease.”

Nearly 3,000 Americans are diagnosed with mesothelioma each year. Finding an effective way to stop the cancer from spreading, as opposed to treating the cancer after it has spread, brings hope to the mesothelioma community.

Find out more about the Scripps study in the January 19 issue of Oncogene.

Sources:

January 19 issue of Oncogene
https://www.nature.com/articles/s41388-017-0075-1
Scripps Research Institute
https://www.scripps.edu/newsandviews/e_20180216/deryugina.html

Mesothelioma Patients Eye Combination Therapy Given FDA Priority Review for Bringing “Significant Survival Benefit” To Lung Cancer Patients

In October 2016, MesotheliomaHelp reported the U.S. Food and Drug Administration approved the immunotherapy drug atezolizumab (TECENTRIQ, Genentech Oncology) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose disease progressed after platinum-based chemotherapy. Now, Genentech reports the FDA has granted priority review for Tecentriq when used in combination with bevacizumab (Avastin), paclitaxel and carboplatin (chemotherapy), for lung cancer patients.

The status was given based on results from the Phase III IMpower150 study, according to the May 6 press release from Genentech announcing the approval. The trial was established to evaluate the safety and efficacy of Tecentriq with the triple drug combination compared with patients receiving the triplet without Tecentriq. Tecentriq is designed to target PD-L1 expressed on tumor cells and tumor-infiltrating immune cells and to enable the activation of T cells, according to the company.

“Our Phase III results showed TECENTRIQ in combination with Avastin, paclitaxel and carboplatin has the potential to provide a significant survival benefit in the initial treatment of metastatic non-squamous non-small cell lung cancer,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “We are working closely with the FDA to bring this treatment regimen to people with this type of lung cancer as soon as possible.”

Lung cancer is by far the leading cause of cancer death among both men and women in the U.S., according to the American Cancer Society. The ACS estimates about 234,030 new cases of lung cancer will be diagnosed in 2018, with approximately 154,050 Americans dying from the cancer. Nearly 3,000 Americans are diagnosed with mesothelioma, with close to the same number losing their lives to it each year.

Pleural mesothelioma is an asbestos-caused cancer affecting the lining of the lungs. Although there are clinical differences between lung cancer and mesothelioma, the treatment protocol for the two cancers are similar. Mesothelioma is a terminal cancer with limited treatment options. Any new breakthrough or approval in the treatment of NSCLC is considered a win for mesothelioma patients as well.

A Priority Review designation will direct overall attention and resources to the evaluation of applications for drugs that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications, according to the FDA.
https://www.fda.gov/ForPatients/Approvals/Fast/ucm405405.htm

A Priority Review designation means FDA’s goal is to take action on an application within 6 months. Genentech reports the FDA is expected to make a decision on approval by September 5, 2018.

Find out more about the IMpower150 clinical trial at ClinicalTrials.gov.
https://clinicaltrials.gov/ct2/show/NCT02366143

Sources :

Genentech
https://www.gene.com/media/press-releases/14715/2018-05-06/fda-grants-priority-review-to-genentechs
American Cancer Society
https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/key-statistics.html

Is It Just A Cough Or Is It Mesothelioma?

Chemicals Identified As Potential Targets for Lung Cancer May One Day Be Focus for Personalized Mesothelioma Treatments

After five years spent testing and retesting over 200,000 different compounds as candidates to be used in the treatment of lung cancer, researchers narrowed the list down to 170 chemicals. Now, the team plans to delve deeper into the mechanisms of the compounds and to assess the effectiveness against other types of cancers. Potentially, mesothelioma and other aggressive cancer patients will benefit from the new discovery.

The team of researchers from University of Texas Southwestern Medical Center, using the Center’s “unique lung cancer cell library,” set out to identify therapeutic triads, according to an April 19 press release. The search required testing against a trifecta of criteria including finding chemicals that kill cancer cells, biomarkers that predict who would respond, and the therapeutic targets on which those active chemicals work.

The 170 chemicals were tested against 100 lung cancer lines to confirm they all met the three sets of criteria. The resulting chemicals are called the Precision Oncology Probe Set, or POPS. This testing approach is considered unusual for cancer research with the team looking at drugs first, then cancers.

“Almost all cancer research is gene-first, or target-first. We began with the potential drugs,” said Dr. Michael Roth, Professor of Biochemistry and a member of the Simmons Cancer Center.

The researchers report that these findings are “a significant step forward toward personalizing cancer care.” They report that for most of the compounds they identified a biomarker that can lead to the development of precision medicine. This means patients with those biomarkers can receive individualized care.

Personalized care targeted to the unique characteristics, such as the biomarkers, of a mesothelioma patient increases the chance of success, and can extend their survival and improve their quality of life. For most mesothelioma patients, life expectancy is less than a year after diagnosis and they often struggle with daily living tasks. There is no cure, and there are limited treatments for the asbestos-caused cancer.

UT Southwestern researchers are known for their innovative approach to cancer research with their findings bringing hope to the mesothelioma community. MesotheliomaHelp has reported on UT’s research into chili peppers in combating cancer and into a new target in fighting the KRAS gene in cancer. They have also conducted mesothelioma clinical trials.

UT Southwestern Medical Center is one of the few institutions in the country with a treatment and research program dedicated to mesothelioma, according to its website. To find out more about UT Southwestern’s research and treatment for mesothelioma, visit the Mesothelioma program’s website.

Read the full study in the March 28 issue of the journal Cell.
https://www.cell.com/cell/fulltext/S0092-8674(18)30308-8

Sources

University of Texas Southwestern Medical Center
http://www.utsouthwestern.edu/newsroom/articles/year-2018/170-lung-cancer-drugs.html
Mesothelioma program’s website
https://utswmed.org/conditions-treatments/mesothelioma/
UT Southwestern Medical Center
https://utswmed.org/conditions-treatments/mesothelioma/

Category: Mesothelioma