Category: Featured News
In the Future, When Cancer Cells Glow Green It’s A Go For Selected Mesothelioma Treatment
Nanotechnology is in the news again with a report that a new technique can determine within eight hours whether chemotherapy is effective for a patient. For mesothelioma patients, and all cancer patients, being able to quickly assess whether a treatment is effective can mean the difference in survival.
According to a March 28 press release from Brigham and Women’s Hospital announcing the findings, a team of researchers found that they can deliver a nanoparticle of a potential cancer treatment that will fluoresce green if the cancer cells die from the drug. The results rely on the enzyme caspase that is activated when a cell dies.
“We can determine if a cancer therapy is effective within hours of treatment,” said co- author Shiladitya Sengupta, PhD, a principal investigator in BWH’s Division of Bioengineering. “Our long-term goal is to find a way to monitor outcomes very early so that we don’t give a chemotherapy drug to patients who are not responding to it.”
One test used paclitaxel chemotherapy on a prostate cancer line. The test realized “an approximately 400 percent increase in fluorescence” in the tumors that were responsive to paclitaxel compared to those cells that were paclitaxel-resistent. The technology was also successful for monitoring the effectiveness of immunotherapy. The researchers yielded “a significant increase in the fluorescent signal” in tumors sensitive to the anti-PD-L1 nanoparticles after five days.
Determining the appropriate cancer treatment for a patient is a difficult and complex decision for patients and their oncologists. Finding an effective mesothelioma treatment is even more challenging due to the relative rarity of the disease. However, the ability to detect responders, as the researchers refer to an effective treatment, and non-responders, in real-time can spare patients needless treatment and allow the oncologist to quickly adjust the treatment protocol without losing precious time.
“Current techniques, which rely on measurements of the size or metabolic state of the tumor, are sometimes unable to detect the effectiveness of an immunotherapeutic agent as the volume of the tumor may actually increase as immune cells begin to flood in to attack the tumor,” said co- author Ashish Kulkarni, an instructor in the Division of Biomedical Engineering at BWH. “Reporter nanoparticles, however, can give us an accurate read out of whether or not cancer cells are dying.”
The researchers’ next step is to assess the safety and efficacy on humans. There was no indication as to the timeline of when this research can move into a clinical setting.
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.”
The full report of the BWH study can be found in The Proceedings Of The National Academy Of Sciences.
Existing Anti-Cancer Drug May be Effective in Lung Cancer and Mesothelioma Patients
Before oncologists can tackle a patient’s cancer they need to know the type of cancer, of course, but knowing what biomarkers comprise the cancer can lead to treatment with a targeted therapy. Targeted therapy is especially critical for aggressive cancers like mesothelioma and lung cancer. Now, researchers report they have found a genetic marker to help identify lung cancer patients who will benefit from an existing anti-cancer drug, imatinib.
Researchers from the Cancer Research UK, Manchester Institute report the Abelson (ABL) family of nonreceptor tyrosine kinases, ABL1 and ABL2, are “mutated or amplified” in nearly 10% of lung cancer cases. The markers, according to the researchers, are key to tumor growth and could give oncologists another way to identify and treat lung cancer patients.
“Drugs that block the activity of the ABL proteins have been used to successfully treat leukaemia patients, where ABL is overactive,” said Dr John Brognard, who led the study, in the March 22 press release announcing the findings. “However, until now, the role of ABL1 and ABL2 in other cancer types hasn’t really been explored.”
The researchers found that ABL1 mutations helped lung cancer cells thrive. However, when the ABL inhibitor, imatinib, approved by the U.S. Food and Drug Administration for leukemia and certain GI tumors, was applied in the lab, it effectively blocked tumor growth.
A 2008 study by researchers in Italy found that imatinib “enhances the therapeutic response to gemcitabine” in combination treatment for malignant mesothelioma.
Pleural mesothelioma, an asbestos-caused cancer of the lining of the lungs, is often treated with similar protocols as lung cancer. Both cancers have shown to be aggressive and often reject and defeat many of the common treatments. However, care that focuses on a patient’s unique traits, such as specific biomarkers like ABL1, allows the oncologists to personalize treatment.
Medical care targeted to a patient’s unique characteristics and genetic makeup optimizes the potential for success of the treatment and offers treatment options that may not otherwise have been considered.
“Drugs like imatinib are already commercially available,” says Dr. Brognard. “This means that we now have an extra ready-made tool for the treatment of lung cancer – we just need to identify which patients will benefit by doing some additional tests.”
“Holy Grail of Medicine” Could Bring a New Way To Treat Mesothelioma
Cancer researchers have been focusing much of their attention on using nanotechnology to deliver cancer-fighting drugs directly to cancerous cells, thus, leaving healthy cells intact. Australian researchers have developed an approach much like the Trojan Horse delivery method Mesothelioma Help reported on last month, but the researchers are touting their method of deploying nanotechnology to kill cancer cells as the “holy grail of medicine.”
Researchers at Flinders University in South Australia are making this claim, and adding that this will revolutionize the way cancer is treated, due to the “smart packages” ability to attack and destroy cancer cells “more efficiently and reduce side effects.” The unique packages contain folate molecules that are attracted to cancer cells that have a lower pH level than healthy cells.
“The way we have designed the vehicle is that you can use it for any number of different cancer cells or combination of different cancer cells,” said Professor Colin Raston, co-lead of the research, according to a March 24 The Lead South Australia article. “You can load it up and target them using specific types of drugs, which we know are for those particular cancers.”
The researchers developed the anti-cancer delivery mechanism that is just 100 nanometres in diameter, or nearly 800 times finer than a human hair, according to the report. Inside the package is a dose of chemotherapy, that, when it finds the cancer cell with low pH levels, “it becomes unstable and delivers the anti-cancer drug inside,” Professor Raston said.
Raston adds that because of the unique way the package binds to the cancer cells, less of the drug is needed “shutting down all the side effects.”
Side effects from the often toxic doses of chemotherapy required to kill cancer cells are well-known and can be debilitating to many patients. For mesothelioma patients who are already in a weakened state, finding a way to bypass the nausea, low blood count, and fatigue can make a difference in the patients’ attitude and survival.
Mesothelioma is a serious cancer that occurs in individuals exposed to airborne asbestos fibers. Although there is no cure for mesothelioma, it can be treated with varying degrees of success through the use of surgical procedures, chemotherapy and radiation.
The research was conducted in a lab on lung cancer treated via a paclitaxel-laden smart package. Paclitaxel is used by some oncologists, typically in combination with another anti-cancer drug, for lung cancer and mesothelioma.
The researchers concluded, this approach “can significantly enhance the utility of nanoparticle delivery technology to tumours.” They added that animal experiments will need to be conducted to assess the “feasibility and safety” of the approach.
The study was published in the March 24 issue of Scientific Reports.
http://www.nature.com/articles/srep23489
Mesothelioma Research May Benefit From Discovery That Silences Metastasis
Mesothelioma cancer cells thrive by splitting and dividing, resulting in metastasis of the cancer to other organs. Stopping tumor growth and preventing metastasis, especially in mesothelioma and lung cancer that are both highly aggressive and resistant to many cancer treatments, is critical for increasing survival in patients. Now, researchers report they have found a key molecule in lung cancer cells that can halt metastasis.
Researchers at Imperial College London report, in a March 21 press release, the MARK4 protein enables cancer cells to split off from its tumor of origin and move to other parts of the body. However, they also found that the miR-515-5p molecule interferes with the production of MARK4. In effect, the molecule “silences” the production of MARK4, preventing the cancer cells from migrating.
http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_21-3-2016-14-56-5
“The ability of a cancer to spread around the body has a large impact on a patient’s survival,” said Professor Justin Stebbing, senior author of the study from the Department of Surgery and Cancer at Imperial. “However, at the moment we are still in the dark about why some cancers spread around the body – while others stay in one place. This study has given important insights into this process.”
It is cancer metastasis, and not the original cancer diagnosis itself, that is the cause of nearly all cancer deaths. In fact, according to various studies, 90 percent of all cancer deaths are due to metastasis. The American Cancer Society reports lung cancer can spread to almost any organ of the body, but most often it will spread to the adrenal glands, liver, bones, or brain. It can also spread to the other lung.
The Imperial College researchers looked at breast and lung cancers and found that reduced miR-515-5p and increased MARK4 levels in both of the cancers correlated to poor patient prognosis. They then increased the amount of miR-515-5p in mouse models using human breast cancer and lung cancer cells and found the higher level of the molecule prevented the spread of cancer cells.
The researchers next step is to assess if the MARK4 protein or the silencer molecule (miR-515-5p) should be anti-cancer drug targets. In addition, the team is investigating whether developing a test for the miR-515-5p molecule could provide a tool to indicate the likelihood of metastasis.
“These findings could have profound implications for treating breast and lung cancers, two of the biggest cancer killers worldwide,” said Dr. Olivier Pardo, lead author of the paper, also from the Department of Surgery and Cancer at Imperial.
Mesothelioma, a rare form of cancer caused by exposure to airborne asbestos fibers, can spread throughout the body by entering the blood stream or the lymphatic system. Due to the aggressive nature of the cancer, it is rare that mesothelioma cells remain confined to the site of origin and have not invaded neighboring tissue through metastasis. Research of this type brings hope to the mesothelioma community that new, effective treatments will soon be available.
See the Feb. 10 issue of the journal EMBO Reports for the full results of the study.
http://onlinelibrary.wiley.com/doi/10.15252/embr.201540970/suppinfo
UK Researchers Identify Drug To Target Mesothelioma Cell Death
Mesothelioma is known to be a resilient cancer due to its aggressive nature and its ability to fight off the very drugs meant to halt its progression. Its resistance to drugs is attributed to its apoptotic defect, which prevents the medicines from killing the cancer cells. Now, researchers report a new drug can bypass that defect and induce cell death.
Researchers from the University of Bradford, in collaboration with researchers from University of Surrey, report cancer cells should die when signals from the immune system and healthy cells tell them to do so. According to the researchers, though, cancer cells have a variety of strategies to ignore those signals and elude death.
“We already know that it’s [mesothelioma] resistant to available drugs, which is why we need entirely new treatments,” says Professor Richard Morgan, from the University of Bradford’s Institute of Cancer Therapeutics, in a March 14 press release.
The drug, known as HRX9, however, works by preventing the cancer cells from avoiding apoptosis. HRX9 targets the HOX gene family that helps to determine cell identity during development. These genes “are significantly dysregulated in malignant mesothelioma,” according to the researchers. When dysregulated, in effect the gene “switch” remains on allowing cancer cells to grow. This drug impacts that switch, and leads to the cells’ death.
“There’s a range of drugs which try to force apoptosis in different cancers, but this is the first one to work in mesothelioma, ” says Morgan.
In the study, the researchers found that human mesothelioma tumors in mice models stopped growing after just three weeks of treatment with HRX9. The tumors had “a complete loss of tumour blood vessels and widespread cancer cell death.”
“People living with mesothelioma often tell us that among their first reactions to diagnosis is despair at the lack of treatment available,” said Ian Jarrold, Head of Research at British Lung Foundation. “We hope that the progress being made in research we fund will soon provide new treatments and new hope for patients.”
The study was published in the Feb. 11 issue of BMC Journal.
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