Signaling Protein Could Lead to New Mesothelioma Treatment

Researchers continue to be confounded by the ability of mesothelioma cells to outfox even the most toxic of anti-cancer treatments. Regardless of the therapy used, the cancer almost always recurs locally. Now, researchers focusing on the P2X7 receptor, that allows cancer cells to communicate, may have found a new target for treating mesothelioma.

Tumors use a complex communication mechanism, known as pathways, to promote their survival. Whereas apoptosis, the natural process whereby damaged cells naturally die, should keep illness at bay, a defect in this process can lead to uncontrolled mesothelioma growth. The P2X7 (P2RX7 or P2X7R) purinergic receptor, or signaling pathway, has been gaining attention due to its involvement in cancer cell death or proliferation.

Researchers from University of Ferrara, Italy have also turned their mesothelioma research focus to the proteins. They found that the P2X7R protein was overexpressed in three different mesothelioma lines derived from previously diagnosed mesothelioma patients. But, they found that the protein was not present in mesothelial cells from healthy patients.

The researchers introduced selective P2X7R inhibitors to the mesothelioma cells and were able to halt the growth of the mesothelioma cells. They then tested the inhibitors on mice with mesothelioma tumors by implanting them under the skin and in the peritoneal cavity. Once again, the treatment resulted in a reduction of tumor growth.

“Our findings suggest that the P2X7R might be a novel target for the therapy of mesothelioma,” concluded the researchers.

Mesothelioma is diagnosed in close to 3,000 Americans each year. Currently, there is no cure for the cancer although patient survival and quality of life can be improved through surgery, radiation and chemotherapy. For patients receiving targeted care, their treatment protocol is often driven by the presence of the cancer’s unique biomarkers.

Read the full study in the July 6 edition of Oncotarget.

New Research Found to Halt Lung Cancer Brings Hope

Lung cancer and pleural mesothelioma are two highly aggressive cancers that are typically diagnosed in a late stage leaving patients with few treatment options. Countless hours of research have been spent on identifying biomarkers or genes that can be targeted to put a halt to the insidious cancers, in the meantime the two cancers continue to take their toll on patients. Now, in a newly released study, researchers report they may have found a way to stop the development of lung cancer.

In an Aug. 5 press release from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore (NUS), researchers reported that by inhibiting the BMI1 protein they could impair tumor growth in lung cancer. Subsequently, the team found that C/EBPα, an important tumor suppressor, has close ties to BMI1, responsible for both tumor growth and survival, and looking at the interaction of the two markers could lead to a novel treatment for lung cancer.

The team of researchers, led by Professor Daniel Tenen, Director of CSI Singapore, discovered that certain non-small cell lung cancers expressed low levels of C/EBPα resulting in poorer survival when a corresponding high expression of BMI1 also existed.

“This study has established an important link between C/EBPα and BMI1 for the first time,” said Prof Tenen. “Furthermore, these findings suggest that assessment of expression levels of these proteins could be used as a way to predict which patients might benefit from drugs which inhibit BMI1, some of which are currently being evaluated in clinical trials.”

Pleural mesothelioma is a rare, serious cancer affecting the lining of the lungs that occurs in individuals exposed to airborne asbestos fibers. Although pleural mesothelioma is distinguished by a large mass of interlocked tumors that blend in with healthy tissue, lung cancer is characterized by more distinct, individual tumors. Despite the differences, any research leading to new treatment for lung cancer brings hope to all of the mesothelioma community.

Nearly 3,000 Americans are diagnosed with mesothelioma each year. The same number succumb to the incurable cancer.

“Therefore, anti-BMI1 pharmacological inhibition may offer a therapeutic benefit for lung cancer patients with low expression of C/EBPα and high BMI1,” concluded the researchers.

The study can be found in the Aug. 3 issue of Science Translational Medicine.

Sources :

Science Translational Medicine
http://stm.sciencemag.org/content/7/284/284ra57
Cancer Science Institute of Singapore
http://www.alphagalileo.org/ViewItem.aspx?ItemId=166813&CultureCode=en

Biomarkers as Diagnosis and Treatment for Mesothelioma

List of Biomarkers Could Lead to Improved Diagnosis and Treatment

A biomarker is a biological molecule found in blood, tissues or other bodily fluids that indicates the presence, or in some cases, the absence, of a particular condition or disease. Biomarkers can be useful in diagnosing and treating mesothelioma, and researchers have been investing large amounts of time and money into this research. Now, thanks to a team of scientists who have compiled a “list of relevant cancer blood biomarkers,” diagnosing and treating mesothelioma patients may soon be easier.

According to an Aug. 1 press release from the University of Sheffield, the scientists, led by Dr. Lesley Uttley, from the University of Sheffield’s School of Health and Related Research, created a comprehensive list of 778 biomarkers that are targets of cancer research. The list, gleaned from over 19,000 scientific studies, could be used to “develop an early stage cancer screening test for the general population.”

“Because of the sheer number of publications in this field, previous reviews have only been able to look at one biomarker or a small group of biomarkers,” said Dr. Uttley. “Our data mining approach allowed us to take in all relevant research findings from the five-year period, which meant we could map the full range of potential blood-based biomarkers that are particularly relevant for early detection of cancer.”

The list that the researchers compiled will be grouped by molecular function as well as including information about the tests and technologies that currently exist to detect the biomarkers. Next, the researchers will group the biomarkers by cancer type, and assess each biomarker and ensure that it “could feasibly be used as part of a screening test.”

Finally, the validated biomarkers will be used in clinical trials to determine how effectively they identify the presence of cancer, and to assess whether the screening tests work effectively and are cost-effective. Prior to the start of the clinical trials, the list will be whittled down to close to 50 biomarkers. The expectation is that this process could take between six and eight years.

“Our vision is that the screen will pick up even the small amounts of these biomarkers that might be in the blood at an early stage of the cancer, without necessarily identifying which cancer they relate to,” said Professor Ian Cree, Early Cancer Detection Consortium Director and Molecular Pathologist at University Hospitals Coventry and Warwickshire NHS Trust. “Patients would then be referred for more specific tests, that could narrow down the tumour type.”

Pleural mesothelioma is a serious cancer caused by breathing in asbestos fibers that then become lodged in the thin membrane that lines and encases the lungs. With no known cure for mesothelioma, an emphasis is placed on early detection and personalized treatment to minimize the impact of this deadly disease on those at-risk.

A reliable method of screening people who have been exposed to asbestos and detecting mesothelioma at an early stage would improve treatment options for patients and improve their quality of life while battling the cancer.

Personalized care targeted to a patient’s unique mesothelioma characteristics optimizes the potential for success of the treatment and offers treatment options that may not otherwise have been considered. Mesothelioma treatments can differ dramatically across patients, and patient-centric treatment that targets the individual’s unique disease characteristics offers the right treatment at the right time.

“Biomarkers play a critical role in improving the drug development process as well as in the larger biomedical research enterprise,” according to a 2011 article from the National Institutes of Health. “Understanding the relationship between measurable biological processes and clinical outcomes is vital to expanding our arsenal of treatments for all diseases, and for deepening our understanding of normal, healthy physiology. “

Nurse Lauds New Mesothelioma Standard of Care

As a result of a clinical trial, there is exciting news that the standard of care for patients receiving chemotherapy for mesothelioma could be changing. Currently, the standard first line chemotherapy for mesothelioma is pemetrexed and cisplatin. It has been the standard since 2003.

What is the new drug that could change all this? Bevacizumab is the generic name, Avastin is the brand name. Avastin was approved for colon cancer by the FDA in 2004 to be used in combination with standard chemotherapy treatment. It works by inhibiting growth of blood vessels, angiogenesis, and was the first clinically used angiogenesis inhibitor.

This news came from the reporting of a clinical trial comparing the standard treatment of pemetrexed and cisplatin with the combination including the addition of bevacizumab. The trials indicated that overall survival and median progression free survival were longer in patients receiving the combination therapy of the three drugs as opposed to the current standard of therapy. The Mesothelioma Avastin Plus Pemetrexed-cisplatin Study (MAPS) trial was conducted by the French Cooperative Thoracic Intergroup (IFCT).

This is an important advance in the treatment of malignant mesothelioma. Together with other advances scientists are slowly putting together the puzzle that is malignant mesothelioma. Avastin is manufactured and distributed by Genentech. If you are a mesothelioma patient that is considering chemotherapy, ask your oncologist if you are a candidate for the new regimen.

Once again, the importance of clinical trial participation and collaboration may have helped progress towards a cure.

The cost of any new medication should not be a barrier to care. There are resources available, including the Genentech’s website, to find out about financial assistance in your use of the drug.

Precision Medicine Initiative for Mesothelioma Community

Mesothelioma Community Will Benefit from Precision Medicine Initiative

In October, Mesothelioma Help presented the National Institute of Health’s plan to fund and manage President Obama’s Precision Medicine Initiative. Now, 18 months after the President made bringing personalized health care to all Americans a focus, the White House has announced “new investments, partnerships, and policies that aim to bring us significantly closer to our goal” of fully utilizing technology and people. The mesothelioma community is watching this initiative geared towards ensuring U.S. patients get the treatments that will work best for them.

Mesothelioma is an asbestos-caused cancer that has few treatment options. However, recent research has turned the focus to personalized care and looking at the disease characteristics as opposed to using the most commonly used treatment protocol. Research has shown this is the best way to increase the survival for patients. This program will help bring tools and technology needed to help researchers continue down this path.

In a July 6 press release from the White House, the three key investments in the Precision Medicine Initiative (PMI) are:

$55 million from the National Institutes of Health (NIH) to recruit the volunteers needed for the PMI Cohort Program;
http://www.nimh.nih.gov/health/topics/depression/index.shtml
A U.S. Food and Drug Administration proposal to streamline its oversight of genomic tests; and,
Development of appropriate tools for researchers to access data.

PMI Cohort Program Gets Boost from Veterans

The ultimate goal of the PMI project is to create a database, through the PMI Cohort Program, 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. The $55 million is ear-marked to help health care provider organizations, technology developers, and community health centers launch the steps needed to recruit volunteers. This information will be used to “lay scientific foundation for precision medicine for many diseases,” according to the NIH.

Nearly 3,000 Americans are diagnosed with mesothelioma each year, and of those, one-third are military veterans. Although many veterans are unaware of this statistic that is a result of their years of service, many have stepped up to the plate once again to help their fellow Americans by allowing science to explore their medical data. As part of the PMI Cohort Program, the VA is partnering with the NIH to help enroll the nearly 500,000 who donated data to the Million Veteran Program, a VA-backed program similar to PMI’s, directly into the PMI Cohort Program and to share the VA’s successes.

Genetic Testing Offers Mesothelioma Patients A Chance at Increased Survival

Personalized medicine is considered the wave of the future, and one of the best ways to combat mesothelioma. Tailored care ensures a mesothelioma patient’s unique disease characteristics, including the cancer’s genetic makeup, are targeted when being treated, thus optimizing the potential for success of the treatment.

The FDA shoulders the responsibility of approving medical tests that identify specific biomarkers, such as the EGFR biomarker often targeted in mesothelioma, to support personalized care. Under the PMI, the FDA is developing “a flexible yet accountable approach to oversight of genomic technologies.” In addition, it will offer a platform and guidelines for researchers to compare the accuracy of their DNA sequencing tests.

“These new policies will make it easier for developers to market safe and effective genomic tests by relying on community-based standards and well-established sources of scientific evidence that meet appropriate standards,” according to the press release.

To find out more about the Precision Health Initiative visit the National Institutes of Health website.

Photo Credit: NCI

Month: August 2016