Category: Featured News
Blood Samples May be Reliable Monitoring Tool for Patients
In January, Mesothelioma Help reported about a business venture by a San Diego-based company focused on developing a blood test to detect cancers that can be conducted in doctors’ offices. Now, another company reports that liquid biopsies, another term for the blood tests, can be used to monitor lung cancer patients’ response to treatment in real-time.
Researchers from the German Cancer Research Center (DKFZ), report that oncologists have come to rely on tissue biopsies as a way to manage a lung cancer patient’s treatment and to assess their progress. However, “tissue biopsy is much more invasive, and in some cases a risky procedure,” they report.
So the researchers delved deeper into the pros of liquid biopsies to help ease pain for patients and to improve the success rates of treatments for oncologists. What they found is that blood tests can be “a promising tool to monitor lung cancer patient tumors early.”
They reviewed the blood samples of 16 EGFR-positive lung cancer patients undergoing tyrosine kinase inhibitor treatment (erlotinib, gefitinib, or afatinib). Over the course of the two-year study the researchers were able to attribute three major categories of treatment to the changes in the circulating tumor cells: evidence for therapy response, periods of stable disease, and impending tumor progression.
“These findings highlight liquid biopsy’s sensitivity in detecting and reflecting tumor changes in real time, while providing the advantages of being less invasive,” said the authors.
The use of biopsy when determining the efficacy of a treatment was previously discussed by a panel of oncologists on OncLive’s Peer Exchange Series. The oncologists agreed that biopsy results can be used to not only diagnose cancer but to drive a cancer patient’s treatment plan. Anne S. Tsao, MD, Director, Mesothelioma Program, The University of Texas MD Anderson Comprehensive Cancer Center, said oncologists should use biopsies to “shoot for genetic testing and personalized medicine for treatment decisions.”
The DKFZ researchers explained that when tumor cells die after treatment they release their DNA (or cell free DNA, cfDNA), with all its mutations still intact, into the bloodstream. The team found that blood samples, or cfDNA, are as effective as tissue biopsies when assessing prognosis in EGFR-positive lung cancer patients.
Professor Holger Sültmann, one of the lead authors, cautions that more work remains to be done, saying, ‘’This is a ‘proof of concept’, we should really collect and measure cfDNA more systematically in order to learn what the liquid biopsy can do under these circumstances, and to fully comprehend the principles of lung cancer progression.’’
EGFR is a protein found on the surface of some cells to which epidermal growth factor binds, which causes the cells to divide and spread. It is found at abnormally high levels on the surface of many types of cancer cells, including more than 50% of pleural mesothelioma patients. Tyrosine kinase inhibitors work by blocking the activity of the EGFR tyrosine kinase enzyme, preventing the growth of new blood vessels that tumors need to grow, and, potentially, killing cancer cells.
Pleural mesothelioma is a cancer of the lining of the lungs caused by past asbestos exposure. The cancer is diagnosed in close to 3,000 Americans each year.
See the Sept. 19 issue of Scientific Reports for the study.
Sources
- Scientific Reports
http://www.nature.com/articles/srep23489 - German Cancer Research Center
https://www.dkfz.de/en/presse/pressemitteilungen/2016/dkfz-pm-16-39-Liquid-Biopsy-Level-of-mutated-DNA-in-the-blood-corresponds-to-patient-outcome.php
WT-1 Vaccine Granted Fast Track Designation for Pleural Mesothelioma
Mesothelioma Help has reported several times on the positive results realized in pleural mesothelioma clinical trials with the WT-1 vaccine. In June, we reported on the “exciting results” from two separate phase II clinical trials for the drug for the treatment of acute myeloid leukemia and malignant pleural mesothelioma. Now, the U.S. Food and Drug Administration has granted fast-track designation to the drug for pleural mesothelioma.
According to a Sept. 19 press release from Sellas Life Sciences Group, the maker of the drug, the FDA granted the status to galinpepimut-S following results of the phase II trial that showed median overall survival was 24.8 months in patients treated with the WT-1 vaccine compared with just 16.6 months in mesothelioma patients who did not receive the treatment. The company reports “survival benefit was even greater” in surgical mesothelioma patients who had the tumors removed and were then treated with galinpepimut-S.
“This fast track designation underscores the importance of galinpepimut-S as a potential treatment option in mesothelioma,” said Angelos M. Stergiou, MD, vice chairman and CEO of SELLAS Life Sciences Group. “We are excited to begin the pivotal Phase 3 trial in patients with MPM [malignant pleural mesothelioma] in the second half of 2017 and expect the Fast Track designation to expedite the time to market, thereby enhancing the value proposition of galinpepimut-S in this indication.”
The fast track designation from the FDA is a process designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need. The purpose is to get important new drugs to the patient earlier, according to the FDA. The agency looks at whether the proposed drug will have an impact on such factors as survival, day-to-day functioning, or the likelihood that the condition, if left untreated, will progress from a less severe condition to a more serious one.
Anne Tsao, M.D., Director of the Mesothelioma Program and the Thoracic Chemo-Radiation Program at The University of Texas MD Anderson Cancer Center, reports through Clinical Care Options online curriculum, that the WT-1 vaccine is one of the up and coming treatments for mesothelioma to keep an eye on. She explains that WT-1, the Wilms tumor protein, is found on mesothelioma cell surfaces making it “an excellent target for immunotherapy.” Galinpepimut-S is a late clinical-stage immunotherapy.
Don Smitley, whose battle with mesothelioma has been chronicled by his daughter Jennifer Gelsick in “Faces of Mesothelioma,” was a participant in the WT-1 clinical trial at Memorial Sloan Kettering. Smitley and his family remained positive throughout the trial and the family continues to Encourage Mesothelioma Patients to participate in mesothelioma trials.
“I believe that we are so close to finding a cure, and the doctors and other researchers we have been so fortunate to work with are among those vitally instrumental in this crusade,” says Jennifer. “Don’t be afraid to step outside of your comfort zone of home and travel for these amazing treatments.”
“Galinpepimut-S is demonstrating its potential as an anti-cancer agent, with outstanding results regarding survival, immunological responses, and safety in AML and MPM patients,” said Dr. Stergiou.
Read about the WT-1 trial results.
Sources :
- Sellas Life Sciences Group
http://sellaslifesciences.com/2016/06/sellas-life-sciences-announces-exciting-results-for-galinpepimut-s-the-companys-wt1-vaccine-in-patients-with-acute-myeloid-leukemia-aml-and-malignant-pleural-mesothelioma-mpm-as-prese/ - fast track designation from the FDA
http://www.fda.gov/ForPatients/Approvals/Fast/ucm405399.htm
Mesothelioma Biomarker Could Lead to “Promising” Treatment
Researchers continue to focus on biomarkers as a target to increase the effectiveness of existing treatments for malignant mesothelioma. These genetic characteristics can be used to indicate the progress of mesothelioma, help determine an appropriate treatment, and assess the effectiveness of that treatment. Now, researchers have identified a biomarker that they believe points to poor prognosis in mesothelioma patients, but that could also lead to a promising therapeutic approach for the asbestos-caused cancer.
Researchers from Japan report the urokinase-type plasminogen activator receptor (uPAR), also known as CD87, that is normally expressed throughout the body, including in the colon and kidneys, was found at elevated levels in a mouse model with mesothelioma. The team from Nagoya University Graduate School of Medicine, Nagoya, Japan, found that the higher the level of uPAR, the worse the prognosis was for the mice.
“For the first time, we showed that uPAR overexpression is observed in asbestos-induced rat MM [malignant mesothelioma], regardless of the asbestos fibers used for carcinogenesis and the histological subtype of MM,” wrote the authors. “These data indicate that uPAR overexpression is a common and important expressional alteration in MM.”
The researchers then went on to discover that overexpression of uPAR is also associated with sensitivity to the platinum-based chemotherapy drug cisplatin. When they blocked the level of uPAR in the mice, there was a rise in the sensitivity to cisplatin. On the contrary, higher levels of uPAR “significantly decreased cisplatin sensitivity.”
According to the National Institute of Environmental Health Sciences, marker levels may be measured before treatment to help doctors plan the appropriate therapy. In some types of cancer, the level of a tumor marker reflects the stage (extent) of the disease and/or the patient’s prognosis (likely outcome or course of disease).
http://www.niehs.nih.gov/health/topics/science/biomarkers/
Mesothelioma is an aggressive, terminal cancer found in the lining of the lungs, heart and abdomen in patients previously exposed to asbestos. Although the cancer has been shown to be chemo-resistant, chemotherapy continues to be one of the primary treatment protocols for the disease, with the preferred combination being gemcitabine and cisplatin.
Patients nearly always develop resistance to chemotherapy, leading to metastasis of the cancer. However, studies like this where research is done to identify ways to increase the sensitivity, and thus the effectiveness, of cisplatin, and potentially other existing treatments, can lead to an increase in patient survival.
“In addition to the potential use of uPAR as a prognostic marker, the combination of uPAR abrogation and cisplatin may reveal a promising therapeutic approach for MM,” the researchers concluded.”
See the Sept. 2 issue of Oncotarget for the full report.
http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=10430
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.
miRNAs Could Be the Key to New, Effective Treatments
Finding a way to stop lung cancer and mesothelioma cells from dividing and growing continues to confound scientists. While many treatments can kill off the cancer cells, there are always some rogue cells that escape death leading to metastasis. Now, researchers report they have discovered a new class of RNA molecules that fuel lung cancer, and targeting them could lead to new, effective treatments for the deadly cancers.
A team of researchers from Singapore report in a July 12 press release they have discovered a new class of microRNAs (miRNAs), called oncomiRs, hidden within cancer stem cells, that drive growth and metastasis of non-small cell lung cancer. The miRNAs, designated as miR-1246 and miR-1290, are “crucial drivers” of tumor growth and progression, the researchers reported.
microRNAs, or miRNAs, are tiny molecules found within cells that serve a function in primary biological processes such as organ development, fat metabolism, cell proliferation and death. When miRNAs function properly, a person remains healthy. However, “disregulation” of miRNAs can lead to diseases, including mesothelioma and other cancers.
The researchers targeted the cancer stem cells, calling them “the major culprits for relapse in lung cancer,” with a new class of therapeutics known as locked nucleic acid (LNA). Using the LNAs they “successfully obliterated human lung tumours grown in mice models.”
MicroRNAs play a large role in the regulation of gene expression and have the potential to serve as biomarkers because they exhibit properties identifiable with specific type of tumors. To that end, the researchers concluded, “these miRNAs [miR-1246 and miR-1290] are clinically useful as biomarkers for tracking disease progression and as therapeutic targets.”
Malignant mesothelioma is a form of cancer that occurs in the thin layer of tissue that surrounds the lungs, abdomen and heart. Asbestos exposure is the only proven cause of mesothelioma. Treatment for the terminal cancer closely follows that of lung cancer. Any breakthrough that leads to a better understanding of the diagnosis, treatment and management of lung cancer brings hope to the mesothelioma community.
Up to 3,000 new cases of mesothelioma are diagnosed in the United States each year. Currently, there is no cure for the disease.
The authors of the study said that the “findings provide fresh insight into understanding therapy resistance in lung cancer and unveil new avenues to monitor and treat the disease more effectively.”
“This will enable scientists and oncologists to improve patient stratification, and to develop therapeutic methods that are targeted, precise, and can reach tumours in the quickest time possible,” said GIS Executive Director Prof Ng Huck Hui.
The team is now collaborating with pharmaceutical companies to develop a drug to be administered to humans.
Results of the study can be found in the June 21 issue of Nature Communications.
Free Mesothelioma Patient & Treatment Guide
We’d like to offer you our in-depth guide, “A Patient’s Guide to Mesothelioma,” absolutely free of charge.
It contains a wealth of information and resources to help you better understand the condition, choose (and afford) appropriate treatment, and exercise your legal right to compensation.
Download Now