Category: Cancer

New Drug Shows Promise for Treating Rare and Aggressive Gliomas

MRI scan showing brain cancer. Credit: Michelle Monje, MD, PhD, Stanford University

An experimental drug may provide a new treatment option for some patients with rare incurable brain tumours, according to an analysis published in the Journal of Clinical Oncology.

Diffuse midline gliomas are diagnosed in about 800 people per year in the U.S., according to the Centers for Disease Control and Prevention.

A subset of particularly aggressive diffuse midline gliomas are caused by a H3 K27M mutation and the only effective treatment is radiation, as the location of the tumour in the brain makes surgery difficult. Even with radiation, relapse is virtually inevitable and more than 70% of patients with this subtype of brain tumour die from the cancer, according to the National Institutes of Health.

In the study, investigators analysed the results of five previous clinical trials testing the effectiveness of dordaviprone, an experimental drug which works by blocking a certain protein in tumours with the mutation.

The study included results from 50 patients (including four children) with H3 K27M–mutant diffuse midline gliomas and found that 30% of patients responded well to the drug. The most common side effect reported was fatigue, according to the study.

Now, the researchers are launching a trial at Northwestern Medicine hospitals to investigate the drug’s effectiveness in newly diagnosed patients.

Source: Northwestern University

Epigenetic Changes Drive this Rare Malignant Paediatric Brain Tumour

A healthy neuron. Credit: NIH

A new study published in Life Science Alliance revealed how aberrant epigenetic regulation contributes to the development of atypical teratoid/rhabdoid (AT/RT) tumours, which mainly affect young children. There is an urgent need for more research in this area as current treatment options are ineffective against these highly malignant tumours.

Most tumours take a long time to develop as harmful mutations gradually accumulate in cells’ DNA over time. AT/RT tumours are a rare exception, because the inactivation of one gene gives rise to this highly aggressive form of brain cancer.

AT/RT tumours are rare central nervous system embryonic tumours that predominantly affect infants and young children.

On average, 73 people are diagnosed with AT/RT in the USA each year. However, AT/RT is the most common central nervous system tumour in children under one years old and accounts for 40-50% of diagnoses in this age group. The prognosis for AT/RT patients is grim, with a postoperative median survival of only 11-24 months.

The collaborative study conducted by Tampere University and Tampere University Hospital examined how aberrant DNA methylation distorts cellular developmental trajectories and thereby contributes to the formation of AT/RT. DNA methylation is a normal process of controlling expression whereby methyl groups are added to the DNA strand, adding epigenetic information.

The new study showed that DNA methylation interferes with the activity of multiple regulators, which usually regulate the differentiation and maturation of central nervous system cells during brain development. Disrupted cell differentiation promotes the abnormal, uncontrolled proliferation of cells that eventually form a tumour.

The study also found several genes that regulate cell differentiation or inhibit tumour development and are silenced in AT/RT together with increased DNA methylation.

“These results will provide deeper insights into the development of AT/RTs and their malignancy. In the future, the results will help to accelerate the discovery of new treatments for this aggressive brain tumour,” says senior author Docent Kirsi Rautajoki from Tampere University.

Source: Tampere University

Scientists Evaluate Old Epilepsy Drug for Glioma Prevention

Photo by Anna Shvets on Pexels

A drug used to treat children with epilepsy prevents brain tumour formation and growth in two mouse models of neurofibromatosis type 1 (NF1), according to a study by researchers at Washington University School of Medicine in St. Louis. NF1 is a genetic condition that causes tumours to grow on nerves throughout the body.

The findings lay the groundwork for a clinical trial to assess whether the drug, lamotrigine, can prevent or delay brain tumours in children with NF1. The study is published online in the journal Neuro-Oncology.

“Based on these data, the Neurofibromatosis Clinical Trials Consortium is considering launching a first-of-its-kind prevention trial,” said senior author David H. Gutmann, MD, PhD, professor of neurology. “The plan is to enrol kids without symptoms, treat them for a limited time, and then see whether the number of children who develop tumours that require treatment goes down.

“This is a novel idea, so we took it to an NF1 patient focus group,” Gutmann continued. “They said, ‘This is exactly what we’re looking for.’ A short-term treatment with a drug that has been used safely for 30 years was acceptable to them if it reduced the chance their children would develop tumours and need chemotherapy that might have all kinds of side effects.”

Optic gliomas, tumours on the optic nerve are the most serious type that those with NF1 get. Such tumours typically appear between ages 3 to 7. Though rarely fatal, they cause vision loss in up to a third of patients as well as other symptoms, including early puberty. Standard chemotherapy for optic gliomas is only moderately effective at preventing further vision loss and can affect children’s developing brains, resulting in cognitive and behavioural problems.

In a previous study, Gutmann and Corina Anastasaki, PhD, an assistant professor of neurology and the first author on the new paper, showed that lamotrigine stopped optic glioma growth in NF1 mice by suppressing neuronal hyperactivity. Intrigued, the Neurofibromatosis Clinical Trial Consortium asked Gutmann and Anastasaki to clarify the connection between NF1 mutation, neuronal excitability and optic gliomas; assess whether lamotrigine was effective at the doses already proven safe in children with epilepsy; and conduct these studies in more than one strain of NF1 mice.

In humans, NF1 could be caused by any one of thousands of different mutations in the NF1 gene, with different mutations causing different medical problems. Repeating experiments in multiple strains of mice was a way of gauging whether lamotrigine was likely to work in people regardless of the underlying mutation.

Anastasaki and Gutmann not only showed that lamotrigine worked in two strains of NF1 mice, they also showed that the drug worked at lower doses than those used for epilepsy, meaning that it was probably safe. Even better, they found that a short course of the drug had lasting effects, both as a preventive and a treatment. Mice with tumours and that were treated for four weeks starting at 12 weeks of age saw their tumours stop growing and even showed no further damage to the retinas. Mice that received a four-week course of the drug starting at 4 weeks of age, before tumours typically emerge, showed no tumour growth even four months after treatment had ended.

These findings have led Gutmann to suggest that a one-year course of treatment for young children with NF1, maybe between the ages of 2 to 4, might be enough to reduce their risk of brain tumours.

“The idea that we might be able to change the prognosis for these kids by intervening within a short time window is so exciting,” Gutmann said. “If we could just get them past the age when these tumours typically form, past age 7, they may never need treatment. I’d love it if I never again had to discuss chemotherapy for kids who aren’t even in first grade yet.”

Source: Washington University School of Medicine

Radon Gas Contributing to Rise in Lung Cancer among Young Adults

Photo by Vladyslav Cherkasenko on Unsplash

Although lung cancer is traditionally thought of as a “smoker’s disease,” a surprising 15–20% of newly diagnosed lung cancers occur in people who have never smoked, many of whom are in their 40s or 50s.

This concerning rise in non-smoking lung cancer cases is likely linked to long-term, high exposures of radon gas. This colourless, odourless gas is emitted from the breakdown of radioactive material naturally occurring underground that then seeps through building foundations. The gas can linger and accumulate in people’s homes and lungs silently unless they know to test for it.

Although the U.S. Environmental Protection Agency (EPA) recommends regular radon testing and corrective measures to lower exposure levels in homes, a new consumer survey conducted on behalf of The Ohio State University Comprehensive Cancer Center (OSUCCC) showed that a stunning 75% of Americans have not had their homes tested for radon, and over half (55%) are not concerned about radon exposure in their homes, community or schools.

“Anyone with lungs can develop lung cancer, and as a community we should be aware and concerned about radon exposure because it’s thought to be one of the leading causes of lung cancer in never-smokers – and there is something we can do reduce our risk,” said David Carbone, MD, PhD, a thoracic medical oncologist. “There are relatively simple tests to measure radon in the home and actions to reduce radon exposure.”

This includes installing outside the home a radon remediation system that sucks air from the basement, where radon gas typically lingers. Increasing air flow by opening windows and using fans/venting in your home, and sealing cracks in the floors, walls and foundation is also important.

Lung cancer rising in young non-smokers

The No. 1 risk factor for lung cancer is long-term cigarette smoking; however, rates of lung cancer among non-smokers continue to rise. The symptoms of the disease are the same regardless of whether the person has smoked: generally not feeling well or feeling tired all the time, frequent cough, chest pain, wheezing, shortness of breath or coughing up blood. These symptoms happen with other illnesses too, but Carbone notes anyone – regardless of age – who has a lingering symptom that doesn’t resolve despite initial treatment should insist on having it checked out.

Lung cancer screening is currently available only to people at the highest risk for the disease – older adults with a history of heavy smoking.

If detected in its earliest stages, the cure rate for lung cancer can be 90–95%. The bulk of cases, however, are not detected until the disease has spread throughout the lung or to other parts of the body, when treatments aren’t as effective. It is important that anyone deemed at risk for lung cancer get timely screening, and that people who might be at increased risk due to secondhand smoke, radon or occupational exposures (like firefighting) talk to their doctors about testing.

“Your health and the health of your family are the most important things you have. Really push to get your concerns addressed if your symptoms aren’t resolving, even if you don’t fit the typical ‘picture’ of lung cancer. It could truly save your life,” said Carbone.

Requiring radon testing in homes, schools and workplaces

Carbone noted that having high levels of radon exposure at school or work is just as much a health hazard as having high-level exposure in your basement.

He says he strongly supports potential legislation to require radon testing at schools, at places of business and during home sales to help reduce community risk. The effects of radon on your lungs is cumulative and can be delayed by decades.

“So your children playing in your basement or going to school today, exposed to unknown levels of radon, could be at risk for developing lung cancer 10, 20, 30 years from now,” Carbone said. “And because the gas is totally colourless and odourless, you would have no idea you were being exposed unless you knew the importance of proactively testing.”

Source: Ohio State University Wexner Medical Center

Approval for First-in Class Glioma Drug set to Change Practice

Photo by Anna Shvets on Pexels

A new drug for the treatment of a type of brain tumour that strikes young people could soon receive approval by the U.S. Food and Drug Administration. The drug, vorasidenib, could greatly extend the time before further therapy – and eventual resistance – is needed.

In an editorial in the New England Journal of Medicine, David Schiff, MD, the co-director of UVA Cancer Center’s Neuro-Oncology Center, outlines the potential significance of the drug vorasidenib for patients with most low-grade gliomas. The drug was fast-tracked by the FDA in August 2023 based on the strength of the findings, and filings for regulatory approval were made in February 2024. FDA approval is anticipated in the second half of 2024, and its approval in Europe will likely soon follow.

Adult-type diffuse gliomas represent approximately 81% of primary malignant brain tumours. Of those, approximately 20% harbour an isocitrate dehydrogenase (IDH) mutation, including 100% of grade 2 and grade 3 adult-type diffuse gliomas. Approximately 2500 Americans with a median age of only 40 are diagnosed with grade 2 IDH-mutant gliomas each year. The tumours cause steadily increasing disability, eventually become resistant to treatment options and typically prove fatal.

 Because of the limited treatment options available, doctors usually take a “watch and wait” approach to managing the brain tumours, holding off on treatment until after the tumour progresses.

In the randomised controlled INDIGO trial, 331 patients received either vorasidenib or placebo. The trial showed that the drug slowed tumour growth significantly and extended the average time until the tumour started growing from 11.1 months to more than 27 months. Vorasidenib also increased the time to next intervention (TTNI), the timeframe before patients need additional treatment such as radio- or chemotherapy. 

Schiff, in his editorial, describes the results as “striking.” Vorasidenib’s success could “put a nail in the coffin” of the watch-and-wait approach for such brain tumours, Schiff believes. 

“It used to be that we thought of all gliomas as being on a spectrum,” Schiff said. “We now understand that those with the IDH gene mutation have a markedly different biology, outcome and, as this study shows, vulnerabilities that new therapies can exploit.”

If the drug receives approval from the federal Food and Drug Administration, it would become the first targeted therapy for low-grade gliomas. But Schiff notes that there are also other recent advances that are improving our understanding of such gliomas.

“There are still many unanswered questions about how we can best utilise this new medication if and when it receives FDA approval,” Schiff said. “Nonetheless, considering that existing standard therapies for these tumours [radiation and chemotherapy] are tough on patients, with short- and long-term side effects, it will be wonderful to have a useful and very well-tolerated treatment option.”

Study Shows no Thyroid Cancer Risk from GLP-1 Agonists

By HualinXMN – Own work, CC BY-SA 4.0,

GLP-1 analogues have become increasingly popular to treat diabetes and obesity, but there have been concerns that they might increase the risk of thyroid cancer. Now an extensive Scandinavian study led by researchers at Karolinska Institutet has found no evidence of such a link. The study is published in The BMJ.

GLP-1 receptor agonists, also known as GLP-1 analogues, reduce blood sugar levels and appetite. They are widely used in the treatment of type 2 diabetes and obesity, with their clinical use steadily increasing. Earlier studies and adverse event data have suggested that these drugs could be associated with an increased risk of thyroid tumours. However, due to limitations in data and methodology, clear conclusions could not be drawn, leading to uncertainty about this potential side effect.

“Many people take these medicines, so it is important to study potential risks associated with them,” says Björn Pasternak, principal researcher at the Department of Medicine, Solna, at Karolinska Institutet in Sweden. “Our study covers a broad group of patients and provides strong support that GLP-1 analogues are not associated with an increased risk of thyroid cancer.” 

The researchers analysed national register data from Denmark, Norway, and Sweden of about 145 000 patients treated with GLP-1 analogues, mainly liraglutide or semaglutide, and 290 000 patients treated with another diabetes drug (DPP4 inhibitors). The risk of thyroid cancer was compared between the groups over an average follow-up period of just under four years. 

GLP-1 treatment was not associated with an increased risk of thyroid cancer. The results were consistent also when compared to a third diabetes medication group (SGLT2 inhibitors).

“We cannot rule out that the risk of certain subtypes of thyroid cancer is increased in smaller patient groups that we could not study here, for example in people with a high congenital risk of medullary thyroid cancer who are advised against using these drugs,” says Peter Ueda, assistant professor at the Department of Medicine, Solna, at Karolinska Institutet.

The ongoing research program at Karolinska Institutet investigates the effects and potential side effects of newer diabetes medications such as GLP-1 analogues and SGLT2 inhibitors. These medications are now being used to treat broader patient groups, including those with obesity, heart failure, and kidney failure.

“We know from randomised clinical trials that they have positive effects, but clinical reality is different with patients varying in disease severity, comorbidities, and adherence to treatment recommendations,” says Björn Pasternak. “It’s therefore essential to investigate how these medicines perform in everyday clinical settings.”

Source: Karolinska Institutet

Bacteria Subtype Linked to Growth in up to 50% of Human Colorectal Cancers

Human colon cancer cells. Credit: National Cancer Institute

Researchers at Fred Hutchinson Cancer Center have found that a specific subtype of a microbe commonly found in the mouth is able to travel to the gut and grow within colorectal cancer tumours. This microbe is also a culprit for driving cancer progression and leads to poorer patient outcomes after cancer treatment.

The findings, published in Nature, could help improve therapeutic approaches and early screening methods for colorectal cancer, which is the second most common cause of cancer deaths in adults in the U.S. according to the American Cancer Society.

Examining colorectal cancer tumours removed from 200 patients, the Fred Hutch team measured levels of Fusobacterium nucleatum, a bacterium known to infect tumours. In about 50% of the cases, they found that only a specific subtype of the bacterium was elevated in the tumour tissue compared to healthy tissue.

The researchers also found this microbe in higher numbers within stool samples of colorectal cancer patients compared with stool samples from healthy people.

“We’ve consistently seen that patients with colorectal tumours containing Fusobacterium nucleatum have poor survival and poorer prognosis compared with patients without the microbe,” explained Susan Bullman, PhD, Fred Hutch cancer microbiome researcher and co-corresponding study author. “Now we’re finding that a specific subtype of this microbe is responsible for tumour growth. It suggests therapeutics and screening that target this subgroup within the microbiota would help people who are at a higher risk for more aggressive colorectal cancer.”

In the study, Bullman and co-corresponding author Christopher D. Johnston, PhD, Fred Hutch molecular microbiologist, along with the study’s first author Martha Zepeda-Rivera, PhD, a Washington Research Foundation Fellow and Staff Scientist in the Johnston Lab, wanted to discover how the microbe moves from its typical environment of the mouth to a distant site in the lower gut and how it contributes to cancer growth.

First they found a surprise that could be important for future treatments. The predominant group of Fusobacterium nucleatum in colorectal cancer tumours, thought to be a single subspecies, is actually composed of two distinct lineages known as “clades.”

“This discovery was similar to stumbling upon the Rosetta Stone in terms of genetics,” Johnston explained. “We have bacterial strains that are so phylogenetically close that we thought of them as the same thing, but now we see an enormous difference between their relative abundance in tumours versus the oral cavity.”

By separating out the genetic differences between these clades, the researchers found that the tumour-infiltrating Fna C2 type had acquired distinct genetic traits suggesting it could travel from the mouth through the stomach, withstand stomach acid and then grow in the lower gastrointestinal tract. The analysis revealed 195 genetic differences between the clades.

Then, comparing tumour tissue with healthy tissue from patients with colorectal cancer, the researchers found that only the subtype Fna C2 is significantly enriched in colorectal tumour tissue and is responsible for colorectal cancer growth.

Further molecular analyses of two patient cohorts, including over 200 colorectal tumours, revealed the presence of this Fna C2 lineage in approximately 50% of cases.

The researchers also found in hundreds of stool samples from people with and without colorectal cancer that Fna C2 levels were consistently higher in colorectal cancer.

“We have pinpointed the exact bacterial lineage that is associated with colorectal cancer, and that knowledge is critical for developing effective preventive and treatment methods,” Johnston said.

Source: Fred Hutchinson Cancer Center

AI-based App can Help Physicians Diagnose Melanomas

3D structure of a melanoma cell derived by ion abrasion scanning electron microscopy. Credit: Sriram Subramaniam/ National Cancer Institute

A mobile app that uses artificial intelligence, AI, to analyse images of suspected skin lesions can diagnose melanoma with very high precision. This is shown in a study led from Linköping University in Sweden where the app has been tested in primary care. The results have been published in the British Journal of Dermatology.

“Our study is the first in the world to test an AI-based mobile app for melanoma in primary care in this way. A great many studies have been done on previously collected images of skin lesions and those studies relatively agree that AI is good at distinguishing dangerous from harmless ones. We were quite surprised by the fact that no one had done a study on primary care patients,” says Magnus Falk, senior associate professor at the Department of Health, Medicine and Caring Sciences at Linköping University, specialist in general practice at Region Östergötland, who led the current study.

Melanoma can be difficult to differentiate from other skin changes, even for experienced physicians. However, it is important to detect melanoma as early as possible, as it is a serious type of skin cancer.

There is currently no established AI-based support for assessing skin lesions in Swedish healthcare.

“Primary care physicians encounter many skin lesions every day and with limited resources need to make decisions about treatment in cases of suspected skin melanoma. This often results in an abundance of referrals to specialists or the removal of skin lesions, which in the majority of cases turn out to be harmless. We wanted to see if the AI support tool in the app could perform better than primary care physicians when it comes to identifying pigmented skin lesions as dangerous or not, in comparison with the final diagnosis,” says Panos Papachristou, researcher affiliated with Karolinska Institutet and specialist in general practice, main author of the study and co-founder of the company that developed the app.

And the results are promising.

“First of all, the app missed no melanoma. This disease is so dangerous that it’s essential not to miss it. But it’s almost equally important that the AI decision support tool could acquit many suspected skin lesions and determine that they were harmless,” says Magnus Falk.

In the study, primary care physicians followed the usual procedure for diagnosing suspected skin tumours. If the physicians suspected melanoma, they either referred the patient to a dermatologist for diagnosis, or the skin lesion was cut away for tissue analysis and diagnosis.

Only after the physician decided how to handle the suspected melanoma did they use the AI-based app. This involves the physician taking a picture of the skin lesion with a mobile phone equipped with an enlargement lens called a dermatoscope. The app analyses the image and provides guidance on whether or not the skin lesion appears to be melanoma.

To find out how well the AI-based app worked as a decision support tool, the researchers compared the app’s response to the diagnoses made by the regular diagnostic procedure.

Of the more than 250 skin lesions examined, physicians found 11 melanomas and 10 precursors of cancer, known as in situ melanoma. The app found all the melanomas, and missed only one precursor. In cases where the app responded that a suspected lesion was not a melanoma, including in situ melanoma, there was a 99.5% probability that this was correct.

“It seems that this method could be useful. But in this study, physicians weren’t allowed to let their decision be influenced by the app’s response, so we don’t know what happens in practice if you use an AI-based decision support tool. So even if this is a very positive result, there is uncertainty and we need to continue to evaluate the usefulness of this tool with scientific studies,” says Magnus Falk.

The researchers now plan to proceed with a large follow-up primary care study in several countries, where use of the app as an active decision support tool will be compared to not using it at all.

Source: Linköping University

Promising Drug Combination for Multiple Myeloma Treatment

Depiction of multiple myeloma. Credit: Scientific Animations

Researchers in Ireland have found that venetoclax, a medication currently approved for leukaemia, has benefits for patients with multiple myeloma when used in combination with another drug. This discovery offers a new avenue of treatment options for the currently incurable disease.

A type of blood cancer, multiple myeloma (MM) is still incurable despite treatment recent advances. The search for innovative treatment strategies is crucial, particularly for patients whose cancer is resistant to standard care.

In the new study published in Haematologica, researchers at the RCSI Department of Physiology and Medical Physics and the Beaumont RCSI Cancer Centre set out to identify complementary drugs that would enhance the efficiency of venetoclax, a drug approved for use in leukaemia, for MM treatment.

Although previously tested in MM, venetoclax, which blocks the function of a protein called BCL-2, was only found to be effective for a small proportion of patients.

The researchers discovered that combining venetoclax with a drug called 5-azacytidine significantly increased its effectiveness across many MM cell lines, indicating a broader potential patient population that could be treated with the new combination.

“This research is a significant step in identifying more effective treatment options for multiple myeloma. By combining venetoclax and 5-azacytidine we’ve seen enhanced efficacy across a wide range of patient samples. It shows the benefits of re-evaluating existing treatments in new contexts to expand their potential.” said Professor Tríona Ní Chonghaile, Associate Professor and research lead, Department of Physiology and Medical Physics.

Professor Siobhán Glavey, Chair, RCSI Department of Pathology and Clinician Scientist, Beaumont RCSI Cancer Centre commented: “Discovering the potential of this new drug combination is a promising development. Our next goal is to test for efficacy and safety for multiple myeloma in a clinical trial setting to bring us closer to offering a new treatment strategy for patients.”

The mechanism of how the two drugs work efficiently together was also investigated and it was shown that the combination of the two therapies was effective in patient samples from different stages of cancer, even if that patient had been previously treated with chemotherapy drugs.

The research was conducted in collaboration with the Department of Haematology, Beaumont Hospital, Dublin; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston; and the Department of Medicine/Haematology, University of Galway, Galway.

This study was supported by funding from Leukemia Research Foundation, Breakthrough Cancer Research and AbbVie.

Source: RCSI

Is it Time for the International Definition of Triple-negative Breast Cancer to be Revised?

Photo by National Cancer Institute on Unsplash

An analysis of Swedish data, where the definition of triple negative breast cancer (TNBC) differs from that used internationally, brings additional insights to on ongoing discussion in the scientific community. The study was presented at the 2023 European Society for Medical Oncology (ESMO) meeting and is now published in Lancet Regional Health – Europe.

The Swedish definition of TNBC differs from the international version in that it also includes tumours with low expression of the Oestrogen Receptor (ER) biomarker, ie in 1–9% of tumour cells. Internationally, ER-low breast cancer is classified as hormone-sensitive and treated differently from TNBC patients. This is despite previous studies demonstrating that the majority of ER-low tumours are molecularly similar to ER-zero, the latter completely without expression of ER, and meta-analyses that show no survival benefit from endocrine therapy in ER-low tumours.

The Swedish population-based study included all women diagnosed with TNBC in Sweden during 2008–2020 using the National Quality Register for Breast Cancer. Patient and tumour characteristics, treatment and survival in patients with low ER expression was compared to patients with no ER tumour expression.

The study identified and included 5655, and 560 patients (10%) were defined as ER-low and 5095 (90%) as ER-zero. The data demonstrated there are only small differences in tumour characteristics, no differences in response to neoadjuvant chemotherapy and no significant differences in prognosis.

“The international cut-off for ER-positivity and thus the definition of TNBC as only completely ER-negative is now increasingly questioned. ER-low tumours behave like ER-zero tumours and should be treated as such. On the basis of real-world data, the Swedish cutoff for hormone receptor positivity appears to be more clinically relevant. A changed international definition would give patients with ER-low expressing breast cancer the same treatment options as in TNBC, within studies and in clinical routine,” says study leader Dr Irma Fredriksson.

The study was carried out in collaboration with the pharmaceutical company MSD.

Source: Karolinska Institutet