Category: Featured News
Researchers Report the EGFR Gene Found in Mesothelioma Silences Tumor Suppression Leading to Uncontrolled Growth
The epidermal growth factor receptor (EGFR) gene has been the focus of researchers for finding new, effective treatments for both lung cancer and mesothelioma patients. The gene, that is overexpressed in more than 50% of pleural mesothelioma patients, and in approximately 15% of lung cancer patients, is one of the primary targets for bringing personalized care to the cancer patients. Now, researchers report they understand just how the gene impacts cancer growth.
Researchers from Yale are referring to the EGFR gene as the “silencer” gene, because, they say, it “silences genes that typically suppress tumors.” The team, led by Narendra Wajapayee, assistant professor of pathology and a member of Yale Cancer Center, report in a June 23 press release, that this critical finding “may lead to the development of more effective, individualized treatment for patients with lung cancer and other cancer types.”
Wajapayee and the team found that EGFR negatively regulated the TET1 protein, important for controlling gene expression and required to suppress tumors, allowing the cancer cells continue to grow and divide.
“EGFR can target multiple unrelated tumor suppressor genes in different cancer types using a common mechanism,” said Wajapayee.
Approximately 2,500 to 3,000 Americans are diagnosed with mesothelioma, an asbestos-caused cancer, each year. Most people diagnosed with mesothelioma are retired workers and veterans who were exposed to asbestos in a workplace or during military service decades ago. The most common form of the cancer is malignant pleural mesothelioma, affecting the lining of the lungs. Disease symptoms can take between 15 and 60 years to appear.
Mesothelioma often resists standard treatments and can build up a resistance to the powerful chemotherapy drugs used to attack the aggressive cancer. Although even targeted EGFR inhibitors can eventually become ineffective, personalized cancer treatment targeted to the unique characteristics of the patient optimizes the potential for success of the treatment.
“The finding informs the future direction of research and treatment of patients who don’t respond or develop resistance to drugs that inhibit EGFR,” said Wajapayee . “It will also help determine how effective cancer therapies will be against different EGFR mutations.”
The results of the study can be found in the June 23 issue of Cell Reports.
Sources:
- Researchers from Yale
http://news.yale.edu/2016/06/23/silencer-study-reveals-how-cancer-gene-promotes-tumor-growth - Cell Reports
http://www.cell.com/cell-reports/fulltext/S2211-1247(16)30700-8
Liquid Biopsies Continue March Towards Use as Diagnostic Tool
MesotheliomaHelp has reported several times over the last year about the promising cancer detection process referred to as a “liquid biopsy.” By using a blood test, as opposed to conducting a traditional biopsy requiring a painful process to remove tissue, researchers report they can detect a specific mutation in a specific cancer to drive treatment. Now, researchers report they are one step closer to developing a blood test that can detect nearly any mutation in cancer.
In a June 6 press release, Guardant Health, along with Samsung Medical Center (Sungkyunkwan University School of Medicine, Korea), reports success with the NEXT-2 clinical trial of 200 advanced cancer patients. The study that used liquid biopsy to test the feasibility of using it “as the sole diagnostic tool” to guide oncologists in matching patients to therapies for multiple cancers, “demonstrated high actionability in matching patients to targeted therapies, as well as statistically significant response rates in lung (88%) and gastric (60%) cancers.”
“The results we have seen have been outstanding, and have certainly exceeded our expectations,” said Dr. Jeeyun Lee at Samsung Medical Center, the primary investigator on the study.
The NEXT-2 trial used the Guardant360 technology – the first and only liquid biopsy that covers all 70 guideline-recommended biomarkers in a single test, according to Guardant. Next up for Guardant is to refine their technology to show that it can effectively spot previously undetected cancers in high-risk patients, such as smokers. Potentially, this technology can be used in other high-risk patients like those previously exposed to asbestos, to detect mesothelioma.
In addition, in a June 4 article in Time, Guardant reported encouraging results from a study of 15,000 patients who were tested with Guardant360. The team was able to identify cancer mutations in over two-thirds of the patients where existing treatments are available. When compared with a traditional tissue biopsy, the blood tests were 98% accurate.
On June 1, the U.S. Food and Drug Administration announced approval of the first liquid biopsy test to detect the EGFR mutation in lung cancer patients. The cobas EGFR Mutation Test v2, is a companion diagnostic for the cancer drug Tarceva (erlotinib), an EGFR tyrosine kinase inhibitor used to treat lung cancer and mesothelioma.
The FDA notes that tumor DNA actually sheds from a tumor into the bloodstream, allowing a liquid biopsy, or blood test, to be used to detect cancer mutations. Currently, there are no effective non-invasive methods for early detection or treatment monitoring for either lung cancer or mesothelioma. However, a blood test can be used for both detection, treatment monitoring as well as for identifying the appropriate treatment protocol.
“Approvals of liquid biopsy tests make it possible to deliver highly individualized health care for patients,” said Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health. “Liquid biopsies also have the potential to allow physicians to identify patients whose tumors have specific mutations in the least invasive way possible.”
“This is a great day for patients,” said Helmy Eltoukhy, co-founder and CEO of Guardant Health. “With the evidence that liquid biopsies are both concordant with tissue, and useful for treating, clinicians have a tool for genotyping that doesn’t bring with it the cost and potential harm of repeat invasive biopsies.”
Sources:
- Guardant Health
http://www.prnewswire.com/news-releases/first-prospective-clinical-utility-trial-using-comprehensive-liquid-biopsy-to-guide-metastatic-cancer-patients-to-molecularly-matched-therapies-demonstrates-comparable-results-to-tissue-based-testing-300279906.html - U.S. Food and Drug Administration
http://www.mercknewsroom.com/news-release/oncology-newsroom/merck-announces-fda-acceptance-review-mk-3475-biologics-license-appli - (June 4 article in) Time
http://time.com/4357037/blood-test-cancer
Finding Cause of Cancer Metastasis May Lead to New Treatments
MesotheliomaHelp has reported on a variety of studies recently where researchers have delved into the reason for metastasis in cancer. Many of the findings focused on cancer pathways. Now, in a new study, researchers report a pair of molecules may be the reason cancers grow unchecked. For aggressive cancers like mesothelioma that elude treatments, this finding could lead to a new treatment that ends cancer growth.
Researchers from Queen Mary University of London’s Barts Cancer Institute of England, led by Dr Stéphanie Kermorgant, report that they focused their research on understanding how cancer cells can continue to thrive after they break away from the primary tumor – when they are most vulnerable. They knew that integrins, or proteins on the cell surface, use ‘outside-in’ and ‘inside-out’ signaling to anchor cancer cells in place. But, using lung and breast cancer cell cultures from zebrafish and mice, they discovered that once the cancer cells began their metastasis process and were floating the integrins started using ‘inside-in’ signaling, or signaling from within the cell.
“Metastasis is currently incurable and remains one of the key targets of cancer research,” said Dr. Kermorgant. “Our research advances the knowledge of how two key molecules communicate and work together to help cancer cells survive during metastasis.”
They found that the beta-1 and c-Met proteins pair up, and migrate into the floating cancer cell to an area that is typically reserved for signaling cell death. Instead, in the case of floating cancer cells, the proteins’ “inside-in” signaling actually guides the rest of the cells to resist death.
Pleural mesothelioma, a cancer of the lining of the lungs caused by past asbestos exposure, is one cancer that is highly aggressive and spreads quickly to other sites. Survival is typically one year after diagnosis. Research shows that metastasis is the cause of nearly 90 percent of cancer deaths, making it critically important that researchers fully understand how to stop metastasis to increase survival in mesothelioma patients.
The QMUL researchers report that current research for integrins focuses on trying to prevent the anchor from failing, or keeping the cells attached in place and not migrating. However, they plan to prevent the integrin from getting inside the cells in the first place, thus, leading “to the design of better therapies against metastasis and more effective treatment combinations that could prevent and slow both tumour growth and spread.”
“We hope that our support of this exciting research will one day lead to better treatments that can prevent the spread of cancer,” said Dr. Susie Gray, Research and Communications Officer at Rosetree Trust, one of the organizations that provided funding for the research.
2,500 to 3,000 people are diagnosed with mesothelioma each year in the U.S. Mesothelioma takes decades to appear after exposure, but then advances rapidly.
The results of the study can be found in the June 23 issue of Nature Communications.
Photo Credit: Barts Cancer Institute, QMUL
Afatinib Better Than Gefitinib in Extending Survival for Lung Cancer Patients
In January 2015, Boehringer Ingelheim reported results from clinical trials that showed EGFR-expressed lung cancer patients treated with afatinib saw “significantly extended overall survival” over those treated with chemotherapy.” Now, in the latest study, comparing the benefits of afatinib over gefitinib, researchers report afatinib resulted in improved progression-free survival compared with gefitinib.
An international team of researchers, led by Keunchil Park, MD, of Sungkyunkwan University School of Medicine in Seoul, South Korea, reported that although the three anti-cancer drugs gefitinib, erlotinib, and afatinib, have shown “superior” results to platinum-based doublet chemotherapy, no study has done a comparison between the drugs, according to an April 29 article in Cancer Network.
In the LUX-Lung 7 clinical trial of 319 EGFR mutation-positive lung cancer patients, half of the patients were treated with afatinib and the other half received gefitinib. The researchers reported the afatinib patients realized better progression free survival at 24 months at 17.6% vs. 7.6% in the gefitinib patients. The time-to-treatment failure was also better with afatinib, at 13.7 months vs. 11.5 months with gefitinib, and objective tumor response for afatinib was 70% compared to 56% with gefitinib.
“The improved antitumor activity with afatinib noted in this trial might reflect its more potent and irreversible inhibition of EGFR signaling,” the authors wrote. “Our findings suggest that first-generation and second-generation EGFR targeted drugs might not be interchangeable.”
In July 2013, the U.S. Food and Drug Administration granted approval to afatinib, a tyrosine kinase inhibitor that blocks proteins that promote the development of cancerous cells, for patients with late stage non-small cell lung cancer whose tumors express specific types of epidermal growth factor receptor (EGFR) gene mutations. The FDA approved gefitinib, also a kinase inhibitor, for the initial treatment of metastatic EGFR-positive non–small-cell lung cancer in July 2015.
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. According to a 2009 article in Current Drug Targets, EGFR over-expression has been shown in more than 50% of pleural mesothelioma patients. The American Society of Clinical Oncology identified approximately 15% of patients with lung cancer in the U.S. expressing EGFR mutations.
Pleural mesothelioma is a rare, serious cancer affecting the lining of the lungs that occurs in individuals exposed to airborne asbestos fibers. Mesothelioma displays as a large mass of interlocked tumors that blend in with healthy tissue, by contrast, lung cancer is characterized by more distinct, individual tumors. However, the treatments for the two cancers are often similar. Any breakthrough or update in research for lung cancer patients equally benefits mesothelioma patients.
“We believe that these data provide additional evidence to help to inform decision making when choosing a first-line treatment for patients with EGFR mutation–positive NSCLC.”
For more information on the LUX-7 clinical trial see ClinicalTrials.gov.
https://clinicaltrials.gov/ct2/results?term=%22malignant+mesothelioma%22&recr=Open&pg=1
Results of the study were published in the April 12 edition of The Lancet Oncology.
http://secure.jbs.elsevierhealth.com/action/cookieAbsent
Sources:
- Cancer Network
http://www.cancernetwork.com/lung-cancer/afatinib-improves-pfs-vs-gefitinib-egfr-mutated-nsclc - FDA approved gefitinib
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm454678.htm
Celebrate Mesothelioma Survivors Every Day
June 5 was National Cancer Survivors Day, a day set aside to ” to honor cancer survivors and to show the world that life after a cancer diagnosis can be fruitful, rewarding, and even inspiring.”Although this day has come and gone, chances are high that mesothelioma patients are aware of their cancer every day of the year. It is important that you also set aside time throughout the year to reach out and support a mesothelioma survivor.
June 5 was a day for mesothelioma survivors and their families to join the nearly 14.5 million other Americans, and millions more around the world, who have survived cancer. The day was a day for CELEBRATION for those who have survived, an INSPIRATION for those recently diagnosed, a gathering of SUPPORT for families, and an OUTREACH to the community, according to the National Cancer Survivors Day Foundation who sponsors the day. We encourage all of the mesothelioma community to take the time out to celebrate with mesothelioma survivors and their families – each and every day of the year.
Mesothelioma is a terminal cancer caused by past exposure to asbestos, a known carcinogen. Although there is no cure for the cancer, advances in treatments are helping patients live longer, more productive lives than in the past. These mesothelioma survivors, defined by the National Cancer Survivor’s Day Foundation as anyone living with a history of cancer – from the moment of diagnosis through the remainder of life, show true grit and strength every day while continuing to fight this dreadful disease.
“When most people hear the word ‘cancer,’ they automatically think the worst,” says National Cancer Survivors Day Foundation spokesperson, Laura Shipp in a May 20 press release announcing the day. “But the truth is that more people are living longer and better quality lives after cancer than ever before. National Cancer Survivors Day® is an opportunity for these cancer survivors – and those who support them – to come together and celebrate this new reality in cancer survivorship.”
In a statement on survivors day, Douglas R. Lowy, MD, Acting Director, National Cancer Institute, and Robert T. Croyle, PhD, Director, NCI Division of Cancer Control and Population Sciences, recognized the challenges cancer survivors face every day and acknowledged the role the NCI plays in helping improve survivorship, saying in part:
“As part of the leadership team of the National Cancer Institute (NCI), we also commend the tireless efforts of the researchers who are working to find new and better ways to control and treat cancer more effectively and safely. This is a vitally important task. Although more and more cancer survivors will return to active and productive lives following their cancer diagnosis, for many of them, the long-term physical, psychological, and social effects of cancer and its treatments remain serious and challenging. Recognizing this, survivorship research remains a key component of NCI’s research portfolio.”
The American Cancer Society reports the average survival time for people with mesothelioma, is between 4 and 18 months. However, between five and ten percent of mesothelioma patients will live at least five years after diagnosis.
“Our Foundation hopes that NCSD serves as a call to action for further research, more resources, and increased public awareness to improve quality of life for cancer survivors,” said Shipp.
Sources:
- National Cancer Survivors Day
http://www.ncsd.org/about-us - National Cancer Institute
http://www.cancer.org/cancer/news/features/when-a-friend-has-cancer - National Cancer Survivors Day Foundation
http://www.ncsd.org/_blog/Front_Page_News/post/Press_Release-May2013/
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