Category: Treatments
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
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
Is Watson the Best Approach for Determining Treatment Plans?
Five years ago Watson debuted on Jeopardy! in a matchup with two of the winningest contestants from the show, Ken Jennings and Brad Rutter. Watson proved why he is a “supercomputer” by handily beating the two at the game. At the time, not many of the viewers envisioned that IBM’s artificial intelligence machine would someday be important to their healthcare. Now, Watson is mainstream in TV commercials asking viewers, “How can I help you?” For a mesothelioma patient, the answer might be, “Find the most effective treatment for me.”
Thanks to a partnership between New York’s Memorial Sloan Kettering Cancer Center (MSKCC) and IBM, Watson Oncology may soon be the go-to reference for oncologists, helping drive cancer care for all patients. Watson Oncology’s primary strength lies in the massive database fed with data from MSKCC on how their doctors treat their cancer patients. While this amount of data is nearly impossible for a doctor to analyze, Watson analyzes and assesses the information quickly, placing incredible knowledge at the doctors fingertips. For patients suffering from mesothelioma, a rare, aggressive cancer with few treatment options, Watson might just be the only way to guide oncologists to finding the best evidence-based treatment protocol.
“We are training Watson so oncologists anywhere will be able to make more specific and nuanced treatment decisions more quickly, based on the latest data,” said an MSKCC spokesperson in response to a comment in an article about Watson.
What is Watson Oncology?
Watson is the result of four years of hard work in IBM’s Grand Challenge: “Can a system be designed that applies advanced data management and analytics to natural language in order to uncover a single, reliable insight in a fraction of a second?” Using Jeopardy! as the ultimate test required IBM to build a machine that can interpret natural or human language that relies on the ability to relate pictures, phrases, figures, slang and nuances.
Since then, Watson has grown into a tool and resource for businesses worldwide. When MSKCC oncologist Mark Kris, MD, William and Joy Ruane Chair in Thoracic Oncology at MSKCC, realized the potential Watson could have on patient care, he led a team to build a database for Watson Oncology that could “revolutionize care and research, accelerating progress for people with cancers.”
MSKCC uses their “world-renowned cancer expertise” to drive Watson Oncology to give oncologists access to “individualized treatment options that are informed by medical evidence and our highly specialized experience.”
“I think this is beyond an evolutionary step,” says Dr. Larry Norton, Deputy Physician-in-Chief for Breast Cancer Programs, MSKCC. “I think this is a revolutionary step.”
In addition to MSKCC’s work with Watson, IBM and MD Anderson Cancer Center have also partnered. The partnership builds on MD Anderson’s oncologists’ knowledge to help drive the center’s Moon Shots program with a goal to “rapidly and dramatically reduce mortality and suffering in cancer.” In much the same as MSKCC’s Watson Oncology, MD Anderson’s Oncology Expert Advisor is expected to provide the medical team “with immediate, worldwide access to MD Anderson’s expertise and resources, and to IBM Watson’s technology prowess in quickly extracting crucial insights from large volumes of complex data.”
Expert Insight
Dr. Larry Norton, MSKCC
“This has the potential of totally changing the way we conduct medicine.”
Watson and Mesothelioma
Having what could become a nearly infinite volume of information instantly available makes Watson incredibly valuable. Using computers to help identify how to treat a complex medical condition, like mesothelioma, can improve survival and the patient’s quality of life. Having the information built by two of the most renowned mesothelioma centers in the world, can only mean excellent care for mesothelioma patients.
MSKCC is the world’s oldest and largest private cancer center, and has a team of specialists including surgical oncologists, medical oncologists, radiation oncologists, pathologists, and nurses who deal exclusively with mesothelioma and other thoracic cancers. They are committed to providing the best possible treatments for patients with malignant pleural mesothelioma, and often conduct clinical trials and studies for mesothelioma as they continue to make strides in the treatment of the deadly disease.
The University of Texas M.D. Anderson Cancer Center works hard at achieving their vision of being the “premier cancer center in the world” through their initiatives in the research and treatment of mesothelioma. The cancer center has over 30 specialists on staff that supports their multi-disciplinary approach to treating mesothelioma patients. Their ongoing research and unique initiatives dedicated to finding a cure for mesothelioma makes them one of the few cancer centers in the world with a comprehensive program.
“Cognitive computing in healthcare allows us to use every step, every heartbeat, every checkup, every gene, every prescription,” according to IBM. “IBM Watson Health is helping transform healthcare and leading us to new insights. Helping keep us all healthier.”
To find out more about how Watson can help you in your mesothelioma care see Watson Oncology on MSKCC’s website, or visit MD Anderson’s Moon Shots Program online.
Researchers Find New Way to Treat KRAS Lung Cancer
In March, MesotheliomaHelp reported that two drugs may be better than one when it comes to treating KRAS-positive lung cancer patients. Now, in a new study, researchers report they have found yet another way to tackle lung cancer when the KRAS gene is present.
In a July 28 press release from UT Southwestern, researchers report that the Kirsten rat sarcoma viral oncogene homolog (KRAS) gene, that is responsible for the most aggressive subtype of non-small cell lung cancer (NSCLC) and is found in nearly 30% of all NSCLCs, controls cell division and can drive healthy cells to divide uncontrollably, leading to cancer. The gene is tough and it nearly always fights off treatments building resistance to the drugs.
“Mutant KRAS not only promotes the growth of tumors, but also the survival of established lung cancer,” said Dr. Scaglioni, who leads the Cancer Signaling Laboratory at the Simmons Cancer Center. “Since we have no clinically-relevant effective inhibitors of mutant KRAS at this time, there has been an intense clinical interest in developing a treatment that is proven effective.”
In order to influence the effects of KRAS, the researchers realized they needed to target the ACSL3 gene. The researchers found that it is the ACSL3 gene that keeps cancer cells alive, yet when suppressed, the gene is responsible for cell death. They also found that the ACSL3 gene is “highly expressed” in lung cancer, thus making it critical to find a way to suppress it.
The scientists tested the impact of the ACSL3 gene in the lab using mice and on a human KRAS-positive NSCLC line. In both cases, the researchers proved that “ACSL3 silencing was accompanied by induction of apoptosis,” or cell death. They propose that, “ACSL3 is a target for the development of targeted therapies against mutant KRAS lung cancer.”
“There is an urgent need for discovery of additional targets that inhibit lipid metabolism in cancer cells that could lead to targeted therapies: the discovery of the importance of ACSL3 in lung cancer meets this unmet need,” said Dr. Mahesh S. Padanad, first author of the study.
Although the research was focused on lung cancer, every new breakthrough in cancer research brings hope to mesothelioma patients. Pleural mesothelioma, an asbestos-caused cancer equally as aggressive as NSCLC, is diagnosed in close to 3,000 Americans each year. Currently, there is no cure for the disease and treatments are often considered palliative.
The study was published in the July 26 issue of Cell Reports.
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