Category: Featured News
Protein Could Be Used to Develop Mesothelioma-Fighting Drug
Researchers report they have found an effective way to induce apoptosis, or cell death, and to suppress cancer growth. The team is targeting the BaK protein and has found a way to transform it “into a killer protein” that kills cancer cells. The hope is that this approach will lead to developing drugs that will be effective in fighting treatment-resistant cancers like mesothelioma.
Mesothelioma, an asbestos-caused cancer, like many cancers, is resistant to standard treatments, and, thus, to apoptosis. Apoptosis is often referred to as cell suicide because when cells are damaged they sacrifice themselves to prevent damaging additional cells. However, in cancer, the process goes amok and the diseased cells continue to divide and grow.
According to researchers from the Walter and Eliza Hall Institute of Medical Research, of Melbourne, Australia, the BaK protein, which is central to apoptosis, is present but inactive in healthy cells. But when a cell receives the trigger to die, BaK is activated and helps destroy the cell. In cancer cells that are notorious for tricking the body’s natural defense mechanisms, however, BaK is not activated and apoptosis does not occur leaving the cells unchecked.
The researchers set out to find a way to mimic the action of BaK, or to turn on the trigger to kill cancer cells. They inadvertently found an antibody they were using to simply study BaK, actually bound to the protein and triggered its activation.
“There is great interest in developing drugs that trigger Bak activation to treat diseases such as cancer where apoptosis has gone awry,” said Dr. Ruth Kluck, BSc, PhD, QLD, lead researcher and Laboratory Head of the Molecular Genetics of Cancer. “This discovery gives us a new starting point for developing therapies that directly activate Bak and cause cell death.”
In fact, the researchers are already collaborating with others to develop their antibody into a drug that can take advantage of the BaK protein.
Finding an effective way to prevent cancer cells from evading cancer death by artificially triggering it could increase the efficacy of existing treatments leading to increased survival in mesothelioma patients. Mesothelioma is diagnosed in nearly 3,000 Americans each year, and the same number die from the cancer.
The full report can be found in the May 24 issue of Nature Communications.
Mesothelioma Patients Need More Information to Help Make Treatment Decisions
When patients are faced with a life-threatening illness like mesothelioma, the more information they have the less anxious they feel about the diagnosis. Unfortunately, according to a recent study, terminally ill patients lack even basic information about their illness.
In a study conducted by a research team from Weill Cornell Medicine in New York City, led by Dr. Holly Prigerson, professor of geriatrics, researchers report that of 178 patients who were faced with highly lethal metastatic cancers, just five percent of the patients had “sufficient knowledge about their illness to make informed decisions about their care.”
“Many did not know that they were at the end-stage of their illness or that their cancer was incurable. They were basically making treatment decisions in the dark,” explained Prigerson, who also co-directs the Center for Research on End-of-Life Care at Weill Cornell.
Treatment for mesothelioma, a terminal asbestos-caused cancer, can vary from patient to patient. Primarily, treatment options consist of surgery, chemotherapy and radiation. It is critical for the patients, however, to understand their prognosis and the benefits and risks associated with each of these options to ensure they are prepared for the arduous battle ahead.
According to the researchers, doctors are reluctant to share information about terminal illnesses for fear that they will upset the patients or the patients will view the doctor less favorably. Without the information, though, many patients have a false sense of security and do not even realize they have limited survival.
The researchers concluded that patients who have discussions with their oncologists about prognosis and life expectancy “come to have a better understanding of the terminal nature of their illnesses.” They added that improvement in the area of end-of-life patient/doctor communication can improve patient-centered care.
This research points to the fact that the more knowledge patients have about their illness, the better off they are when it comes to making their own treatment decisions. In fact, previous research has pointed out that an empowered mesothelioma patient is often the best patient for a medical team. When patients are empowered it means they are informed of their disease and their treatment options, and they are willing to take an active role in their treatment.
Managing a disease such as mesothelioma can be overwhelming, but partnering with your physician from the start may be the key to receiving the best treatment. According to a 2002 article on patient empowerment in the Hong Kong Medical Journal, researchers said, “Medical knowledge has long been used in clinical practice for professionals. It is time to shift the balance of power to include patients and their caregivers.”
The study was published the May 23 edition of the Journal of Clinical Oncology.
Know more about Mesothelioma and how you can deal with it.
Mesothelioma Growth May be Slowed by Blocking Glutamine Pathway
Glutamine, an amino acid and one of the primary building blocks for proteins, is vital for providing fuel to cells throughout the body. However, researchers now believe glutamine can also fuel cancer growth and they are targeting it to develop anti-cancer drugs that may someday be used to fight mesothelioma.
Mesothelioma is a rare, incurable cancer that is caused by breathing in, or ingesting, asbestos fibers. Although chemotherapy is the number one treatment modality, nearly every patient builds up resistance to the drug. In fact, according to researchers from the Research School of Biology, The Australian National University, there are 917 different types of cancer, “and many cures work only for a single type of the disease or become ineffective as cancers develop resistance to chemotherapy.”
For that reason, and to try to develop a drug with much less serious side-effects than standard chemotherapy, the researchers looked at glutamine that is a “very common mechanism in cancer cells.” The researchers decided to focus on the “glutomainolysis pathway” to prevent the glutamine from getting to the cancer cells, thus inhibiting the cancer’s growth.
After first attempting to genetically alter cancer cells, which was ineffective, the team found a way to disable the gateway. They were able to turn off “the biochemical alarm” and successfully blocked gateways through which the cancer cells obtained glutamine. In effect, by cutting off the cancer cells fuel supply they starved the cancer cells. This resulted in a 96 percent reduction in the cancer cells’ growth.
“It is an exciting time to do cancer research,” said lead author Angelika Bröer, from ANU Research School of Biology. “We now have precision tools in our hands to manipulate the genome of cancer cells, allowing us to address problems that were difficult to solve previously.”
First, though, they must turn their attention to finding anti-cancer drugs that will block the glutamine pathways and kill off the cancer. They plan to do this using tests they have developed that will use robots to “test tens of thousands of drugs for us over the next year or two.”
By focusing on pathways that can cut off growth of cancer cells, researchers bring hope to the mesothelioma community that a new, effective treatment is on the horizon. Nearly 3,000 Americans are diagnosed each year with the terminal cancer.
For more information on the study, see the April 26 issue of Journal of Biological Chemistry.
Sources :
- The Australian National University
http://www.anu.edu.au/news/all-news/starving-cancer-the-key-to-new-treatments - April 26 issue of Journal of Biological Chemistry
http://www.jbc.org/content/early/2016/04/26/jbc.M115.700534.full.pdf+html
“Exciting” Results in Study of EGFR-Targeting Drug
In November, Mesothelioma Help reported the U.S. Food and Drug Administration granted accelerated approval for the anti-cancer drug Tagrisso (osimertinib) for lung cancer. This approval opened the door for another mesothelioma treatment as well. Now, researchers report exciting results from a study looking at osimertinib as first-line therapy for epidermal growth factor receptor (EGFR) mutation positive lung cancer patients.
The news of this drug is exciting for several reasons, but primarily for the fact that it demonstrated progression-free survival in first-line therapy. Typically, nearly 50 to 60% of lung cancer patients who experience disease progression after being treated with an EGFR inhibitor often develop the T790M resistance mutation. However, many of the patients in the study “have not had disease progression on the study and are still benefitting from treatment,” according to the researchers.
“The overall response rate was among the best reported for first-line therapy of EGFR-mutated NSCLC,” said Suresh Ramalingam, MD, professor of hematology and medical oncology at Emory School of Medicine and deputy director of the Winship Cancer Institute in Atlanta, in an April 15 press release announcing the findings. “The progression-free survival results are exciting, well exceeding the historical control rates of 10 to 13 months with first- or second-generation drugs.”
In the study of 60 patients with EGFR mutatated non-small cell lung cancer, who received osimertinib without having undergone any other treatment, the overall response rate was 77%. In addition, the patients who did have disease progression did not have T790M mutation, leading Ramalingam to suggest the drug is “changing the biology of the disease.”
In a second study, patients realized nearly the same response rate, 71% in this study, in EGFR-mutated/T790M positive lung cancer patients who had progressed on previous EGFR TKI therapy.
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. According to a 2009 article in Current Drug Targets, EGFR overexpression has been shown in more than 50% of pleural mesothelioma patients, and approximately 15% of patients with lung cancer in the U.S. express EGFR mutations. T790M is a genetic mutation responsible for EGFR-TKI treatment resistance. Osimertinib inhibits both EGFR and T790M, according to AstraZeneca, the maker of the drug.
Next, researchers will conduct a phase III clinical trial with approximately 500 patients comparing osimertinib to either erlotinib or gefitinib for front-line therapy. Erlotinib and gefitinib are kinase inhibitors used to treat mesothelioma and lung cancer. According to the press release, results are expected within 18 months.
The information was presented by Suresh Ramalingam, MD, professor of hematology and medical oncology at Emory School of Medicine and deputy director of the Winship Cancer Institute in Atlanta, at the European Lung Cancer Conference 2016 in Geneva.
http://www.esmo.org/Conferences/Past-Conferences/ELCC-2016-Lung-Cancer/News-Press-Releases/Osimertinib-Given-as-First-line-Treatment-May-Alter-Biology-of-EGFR-Mutated-Non-Small-Cell-Lung-Cancer
Mesothelioma Patients to Benefit from Research Confirming Portrazza Improves Survival in EGFR-Expressed Lung Cancer
In December, Mesothelioma Help reported the U.S. Food and Drug Administration approved Portrazza (necitumumab) for first-line treatment of people with metastatic squamous non-small cell lung cancer. Now, researchers confirm necitumumab is most Beneficial to Lung Cancer Patients expressing epidermal growth factor receptor (EGFR).
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, and approximately 15% of lung cancer in the U.S. Necitumumab blocks the activity of EGFR.
In a report presented April 15 at the European Lung Cancer Conference in Geneva, Switzerland researchers analyzed the results of the SQUIRE Phase 3 clinical trial, designed to determine if necitumumab given in combination with cisplatin and gemcitabine will be more effective than the chemotherapy combination alone. The researchers report the addition of necitumumab to the combination chemotherapy improved overall survival and progression free survival by 21%, over patients who did not receive necitumamab.
The SQUIRE clinical trial did not pre-select patients based on whether they expressed the protein. The researchers, however, drilled in on the subpopulation of patients in the trial, and found that of the 982 patients in the trial, 95% expressed EGFR tumors and just 5% had no EGFR protein. They report that there was no benefit to the necitumumab/cisplatin/gemcitabine combination for patients with negative-EGFR tumors.
“Necitumumab is targeted at EGFR so it makes sense that the drug is active in patients with the receptor,” said Dr. Luis Paz-Ares, Chief of medical oncology at the University Hospital 12 De Octubre in Madrid, Spain, lead author. He added, “the drug had no effect when the receptor was absent, presumably because there was no target to bind to.”
Necitumumab is prescribed in combination with the chemotherapy drugs gemcitabine and cisplatin for the initial treatment of squamous NSCLC that has metastasized. Mesothelioma patients are also candidates for the drug as the cancer is often treated with the preferred chemotherapy combination of gemcitabine and cisplatin.
Within the standard framework of cancer treatments, chemotherapy is considered the most effective single modality for the treatment of mesothelioma and is likely to be the most commonly deployed treatment as well. However, mesothelioma is a highly aggressive cancer and often fights off the effects of chemotherapy. Finding a way to increase the efficacy of the drugs brings hope to mesothelioma patients.
“Based on this analysis, the European Medicines Agency has decided that necitumumab is approved only for patients with EGFR expressing tumours,” said Dr. Luis Paz-Ares.
The FDA did not limit its approval to EGFR-positive patients. Necitumumab was approved in November by the FDA for use in non-small cell lung cancer regardless of the presence of biomarkers. The approval opened up another treatment option for mesothelioma patients.
The researchers report additional research and analysis will be conducted with necitumumab and patient populations.
See ClinicalTrials.gov for information about the SQUIRE clinical trial.
Sources :
- European Lung Cancer Conference
http://www.esmo.org/Conferences/Past-Conferences/ELCC-2016-Lung-Cancer/News-Press-Releases/Patients-with-EGFR-Expressing-Non-Small-Cell-Lung-Cancer-Benefit-Most-from-Necitumumab-Added-to-Chemotherapy - SQUIRE clinical trial
https://clinicaltrials.gov/ct2/show/NCT00981058?term=SQUIRE&rank=2
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