Category: Featured News
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.
Based on Results of Prostate Cancer Study, Specialist Centers Most Likely Offer Best Mesothelioma Care
Due to mesothelioma’s relative rarity among the general population, it is recommended that patients seek out a mesothelioma specialist center. Mesothelioma specialists are aware of the latest research and they are able to develop a more informed treatment plan than would a physician who does not specialize in the disease. Researchers at one of the most prominent mesothelioma centers in the world tested this theory on prostate cancer patients and found that those treated at a high-volume radiation center see better survival rates.
Researchers at Brigham and Women’s Hospital looked at records of nearly 20,000 high-risk prostate cancer patients who received radiation at over 1,000 facilities. The data showed that when treated at “higher-volume facilities,” i.e., the top 20 percent by prostate radiation volume, patients consistently had better survival rates than those treated at lower-volume facilities.
“Our paper shows that experience counts,” said Paul Nguyen, MD, a physician researcher in the department of Radiation Oncology at Brigham and Women’s Hospital and corresponding author of the new paper, in a March 14 press release. “For men with aggressive prostate cancer, survival is improved if they receive their radiation treatments at a high volume facility as opposed to a lower volume facility.”
In the case of mesothelioma care, a mesothelioma specialist will develop the treatment protocol and will supervise its implementation, while the patient still meets with his or her personal doctor. Mesothelioma has a unique set of treatment requirements and specialists serve a key role in interpreting and defining the best approach for caring for the patient.
The Medical Team
At a mesothelioma treatment center, several types of physicians can be involved in the treatment of mesothelioma. Often physicians’ specialties will overlap and several doctors may be available to offer treatment and support in the same discipline. Types of specialists that may be included on a team are:
- Oncologists. Medical professional specializing in cancer.
- Thoracic surgeons. Thoracic surgery is the field of medicine involved in the surgical treatment of diseases affecting the thorax or the chest including the lungs, chest wall, and diaphragm.
- Pulmonologists. Physicians specializing in the treatment of diseases of the lungs and the respiratory tract.
- Chemotherapy (oncology) Nurse. The RN or team of nurses responsible for patient assessment, chemotherapy administration and supportive care during the chemotherapy treatment.
- Radiation Therapist. The radiation therapist develops a treatment plan in conjunction with a radiation oncologist, explains the treatment plan to the patient, and administers the radiation.
In addition to the above specialists, many other medical professionals will be supporting the patient’s needs such as nutritionists, pharmacists, and the primary care physician.
“At a higher volume facility, not only will the radiation oncologist will have more experience at designing and delivering the appropriate treatment fields, but the multidisciplinary team of pathologists, radiologists, urologists, and medical oncologists will have greater expertise in making accurate diagnoses and tailoring the systemic therapy regimen to ensure the best-possible outcome for the patient,” said Dr. Nguyen.
The researchers report other cancer datasets are being planned for review “to corroborate the strong effect seen here.”
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.”
Find the full study in the March 15, 2016 issue of the International Journal of Radiation Oncology, Biology, Physics.
http://www.redjournal.org/article/S0360-3016%2815%2926845-9/abstract
Sources:
- International Mesothelioma Program
http://www.brighamandwomens.org/Departments_and_Services/surgery/thoracic-surgery/mesothelioma/default.aspx - (Brigham and Women’s Hospital ) March 14 press release
http://www.brighamandwomens.org/about_bwh/publicaffairs/news/pressreleases/PressRelease.aspx?sub=0&PageID=2299
Trojan Horse Drug Delivery Method Shown Effective in Drug Resistant Cancer May Also Kill Mesothelioma Cells
MesotheliomaHelp has previously reported on a drug delivery method where the drug sneaks up on the cancer cells via a Trojan horse concept. Now, researchers have developed another Trojan horse delivery method where a drug is hidden inside a DNA capsule.
According to researchers from The Ohio State University, using “DNA origami,” where an anti-cancer drug is enclosed in a capsule of folded up DNA, the targeted cancer cells absorbed the medicine inside the capsule and died. The laboratory test was performed against leukemia cells that had built up a resistance against the drug, however, by hiding the drug in the DNA it was once again effective.
“DNA origami nanostructures have a lot of potential for drug delivery, not just for making effective drug delivery vehicles, but enabling new ways to study drug delivery,” said Carlos Castro, director of the Laboratory for Nanoengineering and Biodesign, in a Feb. 23 press release from the University.
In the study, the researchers discovered that when leukemia cancer cells are treated with daunorubicin, a chemotherapy used to treat leukemia, after the cancer has developed a resistance to the anti-cancer drug, the medicine is fought off by being pumped out through the cell walls.
However, the researchers found that when daunorubicin was cloaked within the DNA capsule, the cancer cells actually drew the capsules in mistaking it for food. Once the capsule was inside the cell it broke down flooding the cancer with the drug, effectively killing the leukemia cells.
The technique should potentially work on most any form of drug-resistant cancer if further work shows it can be effectively translated to animal models, according to study co-author John Byrd of The Ohio State University Wexner Medical Center. This is very good news to the mesothelioma community.
Mesothelioma, an asbestos-caused cancer that attacks the lining of the organs, is like many cancers with few effective treatments and no cure. According to many researchers, the likelihood that mesothelioma will build up a resistance to the very drugs designed to combat the cancer is extremely high. The Ohio State researchers believe that their findings can lead to a new drug delivery method that can restore the effectiveness of the anti-cancer drugs.
“Potentially, we can also tailor these structures to make them deliver drugs selectively to cancer cells and not to other parts of the body where they can cause side effects,” said Byrd.
The study was confined to laboratory cells. Results of the research must next be proven in mouse models before testing on human cancers, which could be years down the road.
To find out more about the DNA Trojan horse see the Nov. 19, 2015 issue of Small.
Researchers Identify Mutations in Mesothelioma That Can Lead to Personalized Care
Biomarkers have become the de facto reference for researchers and oncologists when determining mesothelioma diagnosis, treatment, success of those treatments and prognosis. But identifying reliable biomarkers has been challenging, primarily due to the rarity of the disease. Now, researchers at one of the leading mesothelioma centers report they have identified a “spectrum of mutations” found in mesothelioma tumors.
Mesothelioma is a serious and incurable cancer that is diagnosed in just 3,000 Americans each year. The aggressive cancer, known as “asbestos cancer” since it is almost always a direct consequence of past exposure to asbestos fibers, often eludes standard cancer treatments. Through personalized, targeted therapy, with the help of biomarkers, however, patients see improved survival and a higher quality of life.
Researchers from Brigham and Women’s Hospital of Boston hope to bring personalized care to many more mesothelioma patients through their recent discovery of “previously unknown genetic alterations” in mesothelioma tumors. Some of these mutations that are prominent in other cancers, according to the researchers, have available treatments that could benefit mesothelioma patients with those same mutations.
“By studying so many samples, we’ve been able to describe a spectrum of mutations for this rare disease,” says lead author Dr. Raphael Bueno, chief of BWH’s Division of Thoracic Surgery and co-director of the hospital’s Lung Center, in a Feb. 29 press release. “A small number of these mutations have been found previously in other cancers, and drugs have been developed to target these mutations.”
The researchers performed a “comprehensive genomic analysis” on 216 malignant pleural mesothelioma samples, where they compared the DNA and RNA of the mesothelioma samples and normal, healthy samples. According to the press release, the team uncovered more than 2,500 alterations, and identified 10 significantly mutated genes.
Biomarkers play a critical role in improving the drug development process, according to National Institutes of Health researchers, in addition to identifying focused care. The PD-L1 biomarker has been top-of-the-news recently with the successful treatment in mesothelioma patients and melanoma patients who express the biomarker. The immunotherapy drug blocks PD-L1.
Read more about the immunotherapy drugs and mesothelioma.
“When you have a cancer that has a 80 to 90 percent mortality rate within five years of diagnosis, and you discover evidence that a small percentage of people may have actionable mutations, that means that you could reduce mortality,” said Bueno.
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.”
“We plan to continue this important research through investigator-sponsored trials evaluating the potential use of cancer immunotherapies for the treatment of mesothelioma,” says Bueno.
The results of the study can be found in the Feb. 29 issue of Nature Genetics.
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