Category: Mesothelioma
Researchers Identify Proteins to Target to Increase Sensitivity of Mesothelioma and Lung Cancer Treatments
As MesotheliomaHelp has reported countless times before, researchers focus much of their time on biomarkers in mesothelioma and lung cancer patients to help increase the effectiveness of treatment. By targeting the unique characteristics of a patient’s cancer the researchers aim to increase survival. Now, researchers believe ALK, a key gene often targeted with anti-cancer drugs, can be more effective when other proteins are also targeted.
Everyone has the abnormal anaplastic lymphoma kinase (ALK) gene in their cells, but when a part of it breaks off and reattaches in the wrong way, it becomes an abnormal ALK gene leading to out of control cell growth and ALK-positive lung cancer. By blocking the action of the abnormal ALK gene, crizotinib (Xalkori), an ALK-inhibitor, may shrink or slow the growth of tumors, according to Pfizer, the makers or Xalkori. However, some tumors do not respond to the drug or develop resistance to it.
Researchers from Moffitt Cancer Center focused on increasing the sensitivity of lung cancer tumors to ALK inhibitors. The team turned to proteomics to allow a large scale review of proteins so they could “identify potential drug targets that could boost ALK inhibitors and improve patient outcomes”, according to an Oct. 19 article in Medical News Today.
http://www.medicalnewstoday.com/releases/313580.php
They found a host of proteins, 64 of them, could be used to increase sensitivity to crizotinib, and nine of them could do the same for alectinib, another ALK-inhibitor. They eventually narrowed the list down to two “adaptor proteins FRS2 and CC2D1A” that can increase the sensitivity of lung cancers to ALK inhibitors.
“Knocking down either of these two proteins, the scaffolding proteins FRS2 and CC2D1A, sensitized cell lines to the ALK inhibitors crizotinib and alectinib,” wrote the researchers. “Thus, a clinical strategy that inhibits FRS2 or CC2D1A might enhance the efficacy of ALK inhibitors in some patients.”
Crizotinib, or Xalkori from Pfizer, is intended for the treatment of metastatic non-small cell lung cancers (NSCLC) in patients who express the abnormal anaplastic lymphoma kinase (ALK) gene. Approximately 3%-5% of people with NSCLC may test positive for the ALK fusion gene. There is a potential that the marker is also present in certain pleural mesothelioma cases making it a target for treatment.
Pleural mesothelioma is a rare form of lung cancer that invades the outer lining of the lungs called the mesothelium. The only known cause of mesothelioma is through inhalation or ingestion of airborne asbestos fibers. Both NSCLC and mesothelioma are aggressive cancers following equally aggressive, and similar, treatment protocols.
“Collectively, our data set provides a resource that enhances our understanding of signaling and drug resistance networks consequent to ALK fusions and identifies potential targets to improve the efficacy of ALK inhibitors in patients,” concluded the researchers.
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For the full study see the Oct. 18 issue of Science Signaling.
http://stke.sciencemag.org/content/9/450/rs12
Feeling the Love After Losing My Dad to Mesothelioma
The day that my father passed away was a day full of shock, grief, and sadness. These feelings overwhelmed me, and figuring out how to process them seemed to be an insurmountable task. The days and weeks following, it seemed as though I was in a fog. I was lost and trying to make some sense, any sense, of what had just happened. That was when I realized that I needed to look beyond the grief to find the love.
The day that my father passed away was a day full of love, support, and compassion. Within minutes of receiving a call that Dad wasn’t breathing, a friend came to my home to be with me until my husband arrived home from work. After we got the news that he had passed away, we began to make some calls of our own. These resulted in an ocean of love.
When I finally got the courage to pick up the phone, I called one of my dearest friends who was an hour away. I was scared; saying the words out loud that my Dad was gone made it seem more real. She answered, thankfully, and I told her what had happened. I just needed to let someone know, not expecting anything at all. Within an instant, her husband, one of my oldest and closest friends, showed up at my door. He ended up driving us the three hours to my parents’ home only to turn around and make the trip back. That is love.
During this time, our family began to come. No one said a word; they just hugged us and cried. There was nothing to be said, nor was there a need for a conversation. Knowing that they were there for us gave us all that we needed, love.
When we arrived at my parents’ home, we were greeted by more family members who were there to support us. Throughout the next several days, the outpouring of this love was more than I could handle. I never knew that you could feel so much comfort in the wake of inexplicable sadness.
God truly blesses us with exactly what we need at the moment that it is called for. Through all of our hardest times through Dad’s journey with mesothelioma, we were always met with a helping hand, a hug, and a promise of prayer. I can never repay those who were there for my family and me during this time, but when I think about it, I don’t believe they would want us to try. We are surrounded by the most amazing people and I truly thank God for them every day. They were able to help me see the love through the tears.
Know more about Mesothelioma and how you can deal with it.
Dunbar Fall Festival Raises Funds for the Mesothelioma Applied Research Foundation
Sept. 24 was the Dunbar Community Fest, a wonderful day full of food, fun, and fellowship. Each year my family has a raffle booth there to benefit the Mesothelioma Applied Research Foundation. We appreciate all of the work that the committee puts in to make the event so successful each year!
We had 24 items to raffle this year, plus t-shirts, and our Dining with Donnie cookbooks for sale. All of the visitors to our area seemed to really enjoy taking their time placing their raffle tickets carefully in the items of their choosing.
One of my favorite parts of this event is listening to the stories that people come to share about my Dad. There were several gentlemen who worked with him who spoke about his funny nature and gentle spirit. There were others who told stories about adventures they went on with my father, and even one who told me that her first date with her husband was to my parents’ wedding!
All in all, it was a great time, even though I missed Dad through it all. He loved being involved in any project that I would undertake, particularly planning an event. He was so proud of the efforts we did together to raise money and awareness for the mesothelioma community, and I know that he was smiling down on us that day!
Thank you to everyone who helped to make Dunbar Community Fest and our raffle table a wonderful success and for your continued support and prayers for my family!
Know more about Mesothelioma and how you can deal with it.
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
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
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