Category: Featured News
Mesothelioma Patients May Someday Use a Pinworm Drug to Treat the Asbestos Cancer
When looking for a new, effective anti-cancer treatment, researchers often turn to drugs approved by the U.S. Food and Drug Administration for other diseases or conditions. Finding on off-label use for a drug can shorten the research time and cost to market for treatment of other diseases. Researchers are now looking at repurposing a drug approved for pinworms to treat cancer.
According to a Jan. 30 report from NPR.org, researchers at Johns Hopkins University found that mebendazole, used to treat pinworms, parasitic worms that can live in the large intestine, may be effective in fighting cancers, including brain, lung, and potentially, mesothelioma. The team found that when mice that had pinworms, and were implanted with brain cancer cells, were treated with mebendazole the cancer did not develop.
Encouraged by those results and by the fact that other researchers were conducting similar studies for lung cancer and melanoma, the researchers began two Phase I clinical trials to test the drug’s safety and tolerability in brain cancer in children and adults. The drug has been well tolerated, as expected by the decades-old drug used worldwide to treat pinworms.
“Based on the preclinical studies it looks like it has promise,” says Tracy Batchelor, director of the division of neuro-oncology at Massachusetts General Hospital, who is not involved in the research, according to NPR. “The next step is to look for a benefit in a Phase 2 trial.”
A Phase II trial will determine whether mebendazole is effective on the cancer in people. The Johns Hopkins researchers hope to conduct that sort of trial in adult brain cancer patients.
The benefit of an FDA-approved treatment is that it has already been through clinical trials so there are few surprises for patients and physicians. Side effects are well-known and can be managed. One drug’s success in one condition could lead to an equally effective drug in other diseases.
Clinical trials and the use of off-label drugs bring the best options for improved survival to pleural mesothelioma patients. The cancer that is aggressive and terminal has proven to be resistant to many cancer treatments driving researchers to continue to search for improved care.
“It’s not likely that mebendazole or any other single repurposed drug is ever going to cure cancer,” said Bruce Bloom, president and chief science officer of Cures Within Reach, which has helped to fund the Johns Hopkins research. However, NPR reports, there is the possibility that combinations of repurposed drugs could help in the fight against cancer. Bloom adds that results from this research is still years away.
Recent research has increased survival and quality of life for mesothelioma patients, and many hope to get to the point where mesothelioma is managed as a chronic disease.
To find clinical trials where mebendazole is being tested on cancers visit ClinicalTrials.gov.
Lung Cancer Driver Discovery May Lead to Novel Therapy for Some Mesothelioma Patients
Lung adenocarcinoma, the most aggressive subtype of non-small cell lung cancer (NSCLC), comprises nearly 40 percent of lung cancer diagnoses. The KRAS gene is the most significant driver of this cancer, and is also found in some pleural mesothelioma cases. Researchers have been stymied by this tough gene that nearly always fights off treatments building resistance to the drugs. Now, researchers report they have found a “genetic promoter” that drives this type of cancer and could lead to a new anti-cancer therapy.
Researchers from the Mayo Clinic report that the Ect2 gene (Epithelial Cell Transforming 2) is responsible for cytokinesis, cell division, in normal, healthy cells. However, they found that Ect2 was not needed for cytokinesis in lung adenocarcinoma cells, leading them to uncover the other function Ect2 serves in cancerous cells. They found that Ect2 boosts ribosomes, which “manufacture proteins from messenger RNA instructions.”
“Ect2 drives increased synthesis of ribosomal RNA, which in turn gives rise to increased ribosomes,” said Alan Fields, Ph.D., senior author on the paper and a cancer biologist in the Department of Cancer Biology at Mayo Clinic’s Florida campus, in a Jan. 19 press release. “While it’s been known for a long time that tumor cells have elevated ribosome levels, this paper is the first to show that Ect2 supports tumor cell growth by stimulating ribosome biogenesis.”
Pleural mesothelioma is a serious cancer affecting the lining of the lungs that occurs in individuals previously exposed to airborne asbestos fibers. Asbestos is a known carcinogen and is also proven to cause lung cancer and asbestosis, a chronic lung disease. While there are some differences between pleural mesothelioma and lung cancer, such as the fact that mesothelioma displays as a large mass of interlocked tumors whereas lung cancer is characterized by more distinct, individual tumors, the treatments are often similar.
“KRAS-mediated lung adenocarcinoma is a particularly deadly form of lung cancer, in part because attempts to directly target KRAS therapeutically have not been successful in the clinic,” says the study’s lead author, Verline Justilien, Ph.D., an assistant professor in the Department of Cancer Biology at Mayo Clinic’s Florida campus.
“Our current findings reveal a potential novel therapeutic strategy for treating mutant KRAS lung adenocarcinoma cells in which Ect2 is overexpressed,” Dr. Justilien said.
The American Cancer Society estimates about 222,500 new cases of lung cancer and nearly 155,870 deaths from lung cancer in the U.S. in 2017. Close to 3,000 Americans will be diagnosed with mesothelioma this year with nearly the same number dying from the terminal cancer.
Read the results of the Mayo Clinic study in the January 19 issue of Cancer Cell.
A Pair of Proteins Could Lead to a New Lung Cancer or Mesothelioma Treatment
Last month, MesotheliomaHelp reported on early research from the UK where resea
rchers identified the Spns2 gene could reduce metastasis in lung cancer, and, potentially, in mesothelioma. Identifying a gene or protein effective in halting metastasis is a hot research topic, and now, another team of researchers report they have taken a closer look at a two-part protein to assess its ability to slow cancer growth.
Researchers from the Medical University of South Carolina (http://academicdepartments.musc.edu/newscenter/2016/wrangle-rubinstein-lung-cancer.html) knew that the NRP genes, NRP1 and NRP2, are up-regulated in cancer tumors leading to poor patient prognosis. However, the NRP2 protein is comprised of a 2a and 2b isoform, and when the scientists delved deeper into the effects on lung cancer, they found that while the two are “nearly identical” the differences were significant enough to affect cancer progression.
“Whenever we expressed NRP2b the cancer metastasized, and whenever we expressed NRP2a progression and metastasis were suppressed,” said Robert Gemmill, Ph.D. who holds the Melvyn Berlinsky Endowed Chair for Cancer Research at MUSC. “Clearly, with the 2b isoform, we have found something that promotes metastasis.”
Lung cancer and pleural mesothelioma, the signature cancer of asbestos, are both aggressive and both quickly metastasize, limiting survival. Past research has shown that it is this metastasis, not the original cancer tumors, that leads to death in nearly 90 percent of cancer patients. Unlocking the mystery of metastasis is critical for helping patients lead a longer life.
Through various experiments, the MUSC team found that the potent tumor suppressor, SEMA3F, was reduced or lost, while NRP2b was induced, leading to lung cancer progression. They then found that when NRP2b was knocked out, or suppressed, and NRP2a was induced, chemotherapy resistance was limited, and metastasis was limited.
These findings were encouraging to the team and they hope the findings will “open new avenues for potential therapies,” and that other scientists will pick up the research for development of new treatments for lung cancer. Gemmill points out that uncovering the effects of NRP2b could lead to monoclonal antibodies to target the 2b isoform, new immunotherapies, and possibly using NRP2b as a biomarker for predicting patients’ responses to treatment.
“I think a lot of people are going to sit up when they read this article and say, ‘I wonder what it does in my system?'” said Gemmill.
Nearly 3,000 Americans are diagnosed with mesothelioma each year. The cancer is terminal, and the prognosis is often less than 18 months.
Read the full study in the Jan. 17 issue of Science Signaling (http://stke.sciencemag.org/content/9/450/rs12).
World Cancer Day Another Chance to Bring Attention to Mesothelioma
The National Cancer Institute reports 95% of the cancer diagnoses are dependent on choices we make every day, such as food selection, smoking decisions, sun exposure and exercise habits. Making poor choices can negatively impact our ability to age gracefully and to enjoy a full, productive life. Although Americans diagnosed with mesothelioma doubtful had control over the circumstances leading to their disease, raising awareness about all causes of cancer on Feb 4, World Cancer Day, may help prevent others from having to deal with the devastation that comes with a cancer diagnosis.
Nearly 8.2 million people across the globe die from cancer each year. Feb 4 is one day that is set aside every year to “spread the word and raise the profile of cancer in people’s minds and in the world’s media,” according to WorldCancerDay.org. With the goal to unite the world’s population in the fight against cancer, the organization hopes that by raising awareness and educating the public about the disease, countless lives will be saved.
“World Cancer Day is a chance to reflect on what everyone can do to reduce the impact of this devastating disease, now, and for the future. We wish it to be a springboard for positive change. Take action for yourself, your organisation or your community/country, as everyone can make a difference and inspire others. ‘We can. I can.’ beat cancer,” noted Professor Tezer Kutluk, President, Union for International Cancer Control (UICC).
For the mesothelioma community, this is another chance to shine a light on the pain and suffering over 3,000 Americans have to deal with each day as they are told they have mesothelioma. The rare, incurable disease, brought on by past asbestos exposure, can take decades for the cancer to develop, primarily impacting military veterans and trade workers.
The World Health Organization (WHO) estimates that 125 million people are annually exposed to asbestos in the workplace. The only sure way to stop the suffering and deaths caused by mesothelioma and asbestos-related disease is by preventing exposure, and WHO has been calling for a ban of asbestos use throughout the world. Once widely used in many applications, asbestos is now classified as a human carcinogen. Although the U.S. government regulates the use of asbestos today, it is still not banned in the U.S., as many mistakenly believe.
One of the primary objectives of World Cancer Day is to reach as much of the world’s population as possible during the day. The organization believes that any action anyone takes to educate others has an impact. Through the campaign theme, “We can. I can.”, everyone is encouraged to get involved in the fight against cancer.
“Join us on World Cancer Day to take action on cancer by making health and well-being commitments, participating in the official ‘Talking Hands’ social media activity and getting involved in hundreds of other awareness raising initiatives that are happening worldwide,” said Kutluk.
FDA Grants Orphan Designation to Investigational Mesothelioma Drug
Boehringer Ingelheim announced in December that the U.S. Food and Drug Administration has granted orphan drug designation to its investigational cancer drug nintedanib for the treatment of mesothelioma.
Malignant pleural mesothelioma, a rare cancer caused by exposure to asbestos, is one of the nearly 7,000 diseases designated as rare, or “orphan,” in the United States. An orphan disease status is assigned to a disease or disorder if it affects fewer than 200,000 Americans at any given time. Mesothelioma is diagnosed in close to 3,000 Americans each year, and nearly the same number die from the asbestos-caused disease. There is no cure for the cancer.
The FDA notes that the Orphan Drug Designation program provides orphan status to drugs and biologics which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases or disorders, or that affect more than 200,000 persons but the companies are not expected to recover the costs of developing and marketing a treatment drug.
According to Boehringer Ingelheim, the maker of nintedanib, also known as BIBF 1120, the drug is an oral triple angiokinase inhibitor which simultaneously inhibits vascular endothelial growth factor receptors (VEGFR 1-3), platelet-derived growth factor receptors (PDGFR) and fibroblast growth factor receptors (FGFR 1-3) signaling pathways. These three different angiokinase receptors play an important role in blood vessel formation and in tumor growth and metastases.
Nintedanib “has shown promise as a potential treatment for malignant pleural mesothelioma in clinical trials to-date, and this designation is a validating milestone in its development,” said Martina Flammer, M.D., Vice President, Clinical Development & Medical Affairs Specialty Care, Boehringer Ingelheim in a Dec. 14 press release from Boehringer Ingelheim. “We are proud to receive this designation for nintedanib from the FDA, resulting from our ongoing commitment to researching potential treatment options for rare cancers such as mesothelioma.”
The FDA granted designation based on the positive results from the ongoing Phase II/III LUME-Meso trial. Boehringer reports LUME-Meso is an international trial evaluating the efficacy and safety profile of nintedanib plus chemotherapy (pemetrexed/cisplatin) followed by nintedanib, versus placebo plus chemotherapy (pemetrexed/cisplatin) followed by placebo, in patients with unresectable malignant pleural mesothelioma.
“We are very encouraged by these recent data; the [clinical trial] results have led to an extension of the study into a Phase III confirmatory trial that is now underway and will provide further insight into the potential of nintedanib for patients with MPM [malignant pleural mesothelioma],” said lead investigator, Professor Giorgio V. Scagliotti, University of Torino, Chair of the Department of Oncology, Italy, at the 17th IASLC World Conference on Lung Cancer in Vienna.
Patients are currently being recruited worldwide for the trial. To find out more, see ClinicalTrials.gov.
Sources:
- ClinicalTrials.gov
https://clinicaltrials.gov/ct2/results?term=%22malignant+mesothelioma%22&recr=Open&pg=1 - Boehringer Ingelheim
https://www.boehringer-ingelheim.us/press-release/nintedanib-granted-orphan-drug-designation-treatment-mesothelioma - 17th IASLC World Conference on Lung Cancer
https://www.boehringer-ingelheim.us/press-release/clinically-meaningful-data-oral-nintedanib-mesothelioma-presented-world-conference
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