Category: Featured News
Researchers Identify Mutations in Mesothelioma That Can Lead to Personalized Care
Biomarkers have become the de facto reference for researchers and oncologists when determining mesothelioma diagnosis, treatment, success of those treatments and prognosis. But identifying reliable biomarkers has been challenging, primarily due to the rarity of the disease. Now, researchers at one of the leading mesothelioma centers report they have identified a “spectrum of mutations” found in mesothelioma tumors.
Mesothelioma is a serious and incurable cancer that is diagnosed in just 3,000 Americans each year. The aggressive cancer, known as “asbestos cancer” since it is almost always a direct consequence of past exposure to asbestos fibers, often eludes standard cancer treatments. Through personalized, targeted therapy, with the help of biomarkers, however, patients see improved survival and a higher quality of life.
Researchers from Brigham and Women’s Hospital of Boston hope to bring personalized care to many more mesothelioma patients through their recent discovery of “previously unknown genetic alterations” in mesothelioma tumors. Some of these mutations that are prominent in other cancers, according to the researchers, have available treatments that could benefit mesothelioma patients with those same mutations.
“By studying so many samples, we’ve been able to describe a spectrum of mutations for this rare disease,” says lead author Dr. Raphael Bueno, chief of BWH’s Division of Thoracic Surgery and co-director of the hospital’s Lung Center, in a Feb. 29 press release. “A small number of these mutations have been found previously in other cancers, and drugs have been developed to target these mutations.”
The researchers performed a “comprehensive genomic analysis” on 216 malignant pleural mesothelioma samples, where they compared the DNA and RNA of the mesothelioma samples and normal, healthy samples. According to the press release, the team uncovered more than 2,500 alterations, and identified 10 significantly mutated genes.
Biomarkers play a critical role in improving the drug development process, according to National Institutes of Health researchers, in addition to identifying focused care. The PD-L1 biomarker has been top-of-the-news recently with the successful treatment in mesothelioma patients and melanoma patients who express the biomarker. The immunotherapy drug blocks PD-L1.
Read more about the immunotherapy drugs and mesothelioma.
“When you have a cancer that has a 80 to 90 percent mortality rate within five years of diagnosis, and you discover evidence that a small percentage of people may have actionable mutations, that means that you could reduce mortality,” said Bueno.
Brigham and Women’s is home to the International Mesothelioma Program. Managing over 300 mesothelioma consultations per year, the International Mesothelioma Program is the largest program of its kind in the world. The Program has a mission “to offer state-of-the-art treatment to patients with malignant pleural mesothelioma.”
“We plan to continue this important research through investigator-sponsored trials evaluating the potential use of cancer immunotherapies for the treatment of mesothelioma,” says Bueno.
The results of the study can be found in the Feb. 29 issue of Nature Genetics.
Know more about Mesothelioma and how you can deal with it.
Early Detection Tool for Mesothelioma On the Horizon
Each year, thousands of people in the U.S. and across the world are faced with a diagnosis of mesothelioma. The deadly, aggressive cancer, caused by past asbestos exposure, hibernates for decades before life-threatening symptoms become apparent. The key to increased life expectancy when battling this cancer is early detection. A reliable diagnostic tool, however, has been elusive to researchers until now. In a recent study, researchers report “exciting results” in detecting a protein indicating the presence of malignant mesothelioma.
MorNuCo Laboratories of Indiana, announced last month that with its ONCOblot® Test a team of researchers conducted a retrospective clinical trial where a mesothelioma-specific form of the ENOX2 protein “was found within the serum of asbestos-exposed individuals an average of 6.2 years in advance of clinical symptoms.”
“The completion of this trial is an exciting new chapter for our work,” says Nick Miner, Vice President of Business Development, in the company’s Feb. 4 press release. “Although asbestos-induced mesothelioma is a very specific example of early detection, we are currently pursuing larger-scale clinical trials to investigate the utility of the ENOX2 protein marker to predict the onset of cancers of other tissues of origin as well.”
Although the American Cancer Society identifies chest x-rays, CT scans, PET scans and the bronchoscopy as tests used to diagnose mesothelioma, these are only effective after a patient has presented with worsening respiratory symptoms. MorNuCo’s goal with ONCOblot, is to offer a tool that can detect the cancer early, “before the disease progresses and to begin treatment well in advance of life-threatening symptoms.”
Mesothelioma often has symptoms such as a persistent cough, shortness of breath, fatigue and wheezing, that are similar to many other respiratory illnesses. When a patient presents with these symptoms, doctors often first treat the patient for a respiratory infection before turning to testing for cancer. 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 cancer is detected early.
“The results of this study showed that two mesothelioma-specific ENOX2 protein transcript variants were detected in the serum of asbestos-exposed individuals 4–10 years prior to clinical diagnosis of malignant mesothelioma, an exciting sign of progress in the cancer detection field,” according to the press release.
The study can be found in the Jan. 22 issue of Clinical Proteomics Journal.
Note: Physicians can order the ONCOblot® Test, however, it has not yet been approved by the U.S. Food and Drug Administration. The test is CLIA Certified (Clinical Laboratory Improvement Amendments) and CAP Accredited (College of American Pathologists). The cost of the test is not covered under insurance.
For more information see the FAQs on Oncoblot’s website.
Ease Up On Aggressive Mesothelioma Treatments To Prolong Lives
Just last month, MesotheliomaHelp wrote about how the toxicity of cancer treatments, that kill many healthy cells, may open up new pathways for tumors allowing them to grow and spread. Now, another team of researchers support taking a less aggressive “kill all” approach to prevent the inevitable outcome of treatment resistance.
Researchers at Moffitt Cancer Center in Tampa, Florida, led by Robert Gatenby, M.D., study author and leader of the Cancer Biology & Evolution Program at Moffitt, want to attack cancer with adaptive therapy, which focuses on keeping resistant cells in check by maintaining an army of chemo-sensitive cells alive.
According to a Feb. 24 press release from the cancer center, bombarding cancer with the highest tolerated dose of chemotherapy, the typical approach, may effectively kill cancer cells in the short-term, but chemo-resistant cells escape the treatment and continue to grow and spread.
The old school approach to treatment, especially for mesothelioma, an incurable asbestos-caused cancer, is to take an aggressive approach in fighting the equally aggressive cancer. According to the researchers, however, by giving a lower dose of the chosen chemotherapy and keeping some chemo-sensitive cells intact, they can compete with the resistant cells and stop them from taking over.
“The goal is to enhance the value of therapy by using evolution in our favour rather than letting it beat us,” says Dr. Granby.
The approach, says Dr. Gatenby, adjusts treatment based on the size of the tumors and involves blasting the tumor with a high dose during its growth phase, then reducing the dosage as the tumor shrinks. Through this process, the patient maintains a higher quality of life with the lower toxicity levels, and the cancer is held at bay.
“Our goal is to keep playing this game with the tumour to keep it sensitive, and as long as we do that the patient is alive and fine,” says Granby in a Feb. 24 article in New Scientist. “Then they can have prolonged periods of time when they’re not getting any therapy at all.”
If the cancer recurs, another round of treatment again kills off the bulk of the cancer cells, but allows the patient to maintain a good quality of life. When tested on mice, this approach kept tumors small for much longer, “and after the initial 20 days only low doses were needed to prevent the tumours growing larger.” In addition, “therapy was stopped completely for 60 per cent of the animals, without the cancer progressing.”
The standard treatment protocol for mesothelioma patients is chemotherapy. However, the high doses often leave patients in fragile health from side effects including diarrhea, vomiting and anemia. Any treatment that improves quality of life and extends survival is a welcome approach.
Mesothelioma is responsible for the death of nearly 3,000 Americans each year.
The study can be found in the Feb. 24 issue of Science Translational Medicine.
http://stm.sciencemag.org/content/7/284/284ra57
Sources:
- Cancer Center
https://www.moffitt.org/newsroom/press-release-archive/2016/moffitt-researchers-develop-a-novel-cancer-treatment-approach-based-on-evolutionary-principals-to-inhibit-chemo-resistance-prolong-progression-free-survival - (Feb. 24 article in) New Scientist
https://www.newscientist.com/article/2078806-gentler-attack-on-cancer-may-mean-we-can-live-with-it-for-longer
Groundbreaking Brain Cancer Discovery May Lead To New Mesothelioma Treatment
Glioblastoma, a brain cancer, is highly aggressive and has limited treatment options. Although researchers have been diligent in their work to find a new, effective treatment, there has been no significant breakthrough in treatment for the cancer for decades. Now, researchers believe they may have found a way to turn a patient’s skin cells into cancer killing cells, leading to a “groundbreaking discovery” for brain cancer patients.
Glioblastama is a highly aggressive cancer with cells that quickly reproduce due to the large network of blood vessels found within the brain. Like pleural mesothelioma, the signature cancer of asbestos, glioblastama often has a complex, interwoven growth pattern with finger-like tentacles that spread out causing the boundaries between malignant tissue and healthy tissue to become blurred. Because of this, surgery, often the first course of treatment, leaves cancerous cells behind leading to continued growth and limited survival.
“Patients desperately need a better Standard of Care,” said Shawn Hingtgen, Ph.D., an assistant professor in the UNC Eshelman School of Pharmacy and member of the Lineberger Comprehensive Care Center, who led the study, according to a Feb. 24 press release from University of North Carolina.
http://uncnews.unc.edu/2016/02/24/unc-chapel-hill-researchers-make-groundbreaking-discovery-use-skin-cells-to-kill-cancer/
To achieve this, the researchers report that they found a way to take the patient’s own skin cells and turn them into “cancer-hunting stem cells that destroy brain tumors.” In effect, through a Nobel Prize-winning technique from 2007, the researchers reprogrammed the skin cells to become induced neural stem cells.
These stem cells, according to the researchers, “have an innate ability to move throughout the brain and home in on and kill any remaining cancer cells.” The team also showed that these stem cells could be engineered to produce a tumor-killing protein, increasing the likelihood the cancerous cells will be stopped.
“We wanted to find out if these induced neural stem cells would home in on cancer cells and whether they could be used to deliver a therapeutic agent,” said Dr. Hingten. “This is the first time this direct reprogramming technology has been used to treat cancer.”
In a test on mice, the team was able to increase the survival by as much as 220 percent, depending on the type of tumor. In the short term, the team will turn their focus to human stem cells and assessing anti-cancer drugs that can be loaded into the tumor-seeking neural stem cells.
The team is also focusing on “improving the staying power of stem cells within the surgical cavity.” The work will ensure the stem cells have enough life to seek out the cancer cells.
Breakthrough in any cancer research can translate to hope for the nearly 3,000 Americans diagnosed with the deadly cancer each year. The average survival time for mesothelioma patients is less than a year.
The full study can be found in the Feb. 2 journal Nature Communications.
http://www.nature.com/ncomms/2016/160524/ncomms11734/full/ncomms11734.html
Initial Research That Shows Combination Therapy “Substantially” Improves Lung Cancer Survival Rates Could Translate to Mesothelioma
Recent research into the most effective treatments for lung cancer and mesothelioma patients has led researchers to conclude that two drugs are more effective than one. Now, in another study, researchers found the same to be true, and that a combination therapy significantly increased survival rates in certain lung cancer patients who have limited treatment options.
Read about other combination treatments using immunotherapy here and here.
http://www.asbestosdiseaseawareness.org
Researchers from the Experimental Oncology Group at the Spanish National Cancer Research Centre (CNIO) report lung cancer patients expressing the Kirsten rat sarcoma viral oncogene homolog (KRAS) are faced with the most aggressive subtype of lung cancer. Nearly 30% of the 20,000 lung cancer cases in Spain each year are KRAS-positive, but, according to the CNIO team, the standard treatment is cisplatin-based therapy that has proved inadequate.
The researchers set out to understand how tumors evolve, or as they report, “adapt to the environment in order to grow and survive.” This, they report, is why cancers become resistant to cancer treatments after initially responding.
“Classically, tumours have been studied at advanced stages, but we were interested in studying the initial stages of tumour formation,” says Chiara Ambrogio, first author of the paper, in a Feb. 10 press release announcing the research. “We followed this approach to avoid the heterogeneity issue and try to identify new essential mechanisms that sustain tumour development with potential therapeutic uses,” says Ambrogio.
After nearly five years of research, the team found that the combination of the anti-cancer drugs dasatinib, a DDR1 protein inhibitor, and demcizumab, a Notch pathway inhibitor antibody, worked in concert to “effectively” reduce lung tumors and improve “prognosis and survival rates substantially.”
The researchers concluded that the two drugs were comparable to standard chemotherapy and that it could lead to “an effective targeted therapy for patients with KRAS-mutant lung adenocarcinoma.”
Mesothelioma is a rare form of cancer caused by exposure to airborne asbestos fibers. Mesothelioma is highly aggressive and is resistant to many current treatments. Care often follows the same protocol as lung cancer. Approximately 3,000 Americans are diagnosed with mesothelioma each year. Currently, there is no known cure for mesothelioma.
The research, conducted on mouse models, will soon move into clinical trials “which will make it possible to transfer the discoveries to cancer patients.”
The study was published in the Feb. 8 issue of Nature Medicine.
http://www.nature.com/nm/journal/v22/n3/full/nm.4041.html
Sources:
- Experimental Oncology Group at the Spanish National Cancer Research Centre
https://www.cnio.es/ing/publicaciones/the-cnio-finds-a-potential-therapy-for-the-most-aggressive-type-of-lung-cancer-in-preclinical-models
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