Category: Cancer

Categories : CancerTags :

Less than Half of Community Oncologists Use Biomarker Testing

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A survey found that less than half of community oncologists surveyed indicated using biomarker testing to guide patient discussions, compared to 73% of academic clinicians.

Recent advances have substantially altered the management of lung cancer but, there is a concern these new methods, which include biomarker testing, will not be used equally throughout the health care system and worsen disparities that may already be entrenched.

To determine this, the Association of Community Cancer Centers (ACCC), led by Leigh Boehmer, Pharm.D., chief medical officer, developed a US oncology clinician-facing survey instrument.

To help guide clinicians in the use of biomarker testing, the College of American Pathologists, the IASLC, and the Association for Molecular Pathology published the 2018 CAP/IASLC/AMP Molecular Testing Guidelines for Lung Cancer. Dr. Boehmer reported that of the 99 responses collected, only 40 percent indicated they were “very” or “extremely familiar” with the 2018 Guidelines.

The researchers found that clinicians were most confident in selecting appropriate tests to use, interpreting test results, and prognosticating based on test results, but less confident in determining when to order testing and coordination of care. This lack of communication was echoed in focus groups, Dr Boehmer reported.

Clinicians are most likely to order biomarker testing to make more accurate treatment decisions and inform patient discussions, but only 48% of community clinicians indicated that they use biomarker testing to guide patient discussions compared to 73% of academic clinicians.

Asked about preferences when making a final testing decision, 41% of clinicians prefer that they share responsibility with the patient while 52% prefer to make the final decision themselves. Only 6% prefer that the patient make the final decision. Focus groups suggested that clinicians perceive that patients rarely understand what testing entails and how it affects treatment options.

To make more informed decisions about biomarker testing, clinicians indicated that they need more information on financial resources, as well as education around both published guidelines and practical implications of clinical data. Sixty-seven percent of clinicians provide printed educational materials to their patients. When asked what resources their patients need most, 27% said their patients need handouts or educational resources, followed by psychosocial support (23%) and financial assistance (22%).

“This study identifies key areas of ongoing clinician need related to biomarker testing, including increased guideline familiarity, practical applications of guideline-concordant testing, and how to optimally help coordinate multidisciplinary care,” said Dr. Leigh Boehmer, Pharm.D. “Professional organisations and advocacy groups should focus on developing impactful education materials and tools for improving patient-clinician discussions about biomarker testing.”

Source: International Association for the Study of Lung Cancer

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Elevated Cancer Risk in 9/11 Responders 20 Years On

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Image by David Mark from Pixabay

Associations between responders exposed to toxins at the World Trade Center (WTC) collapse site and increased cancer risk continue to be observed 20 years after the tragic event.

Thousands of rescue workers and first responders were exposed to toxins (asbestos, polychlorinated biphenyls, benzene, dioxins) in the aftermath of the World Trade Center attacks on September 11, 2011. Two studies recently published in Occupational & Environmental Medicine reported on the cancer incidence rates among the WTC Health Program General Responder Cohort.

According to the first study, male New York City firefighters exposed to the WTC site had higher rates of all cancers 13% increase and a younger median age at diagnosis (55.6 vs 59.4 years) compared with male non-WTC-exposed firefighters.

The WTC-exposed firefighters had increased rates of a number of cancers, the highest of which was thyroid cancer (153%) reported Mayris Webber, DrPH, of the Bureau of Health Services at the Fire Department of the City of New York, and colleagues.

The second study from Charles Hall, PhD, of Albert Einstein College of Medicine in the Bronx, and colleagues, found that, beginning in 2007, rescue/recovery workers at the WTC site had a 24% increased risk for prostate cancer compared with the general population in New York State.

Webber and colleagues noted that all firefighters are repeatedly exposed to occupational hazards, including known carcinogens. Their 2016 study found no difference between WTC-exposed firefighters and a group of non-WTC-exposed firefighters from three other cities. The current study extended follow-up to allow for detection of cancers up to 15 years after WTC site exposure.

In this analysis of 10 786 WTC-exposed firefighters and 8813 non-WTC-exposed firefighters, prostate cancer was the most commonly diagnosed cancer among both groups.

In comparison to the US male population, all-cancer incidence among exposed firefighters was “higher than expected”, an increase of 9% even after adjustment for possible surveillance bias.

The researchers adjusted for earlier detection made possible through free screenings, but elevated rates persisted for all cancers (7%), prostate cancer (28%), non-Hodgkin lymphoma (21%), and thyroid cancer (111%).

Webber and colleagues acknowledged that assessment of cancer risk among WTC-exposed firefighters is complex, as “these firefighters were subject to carcinogenic exposures, while also enduring enormous physical and mental burdens related to the attacks.”

“Evidence is slowly accruing about cancer and other long latency illnesses in relation to WTC exposure, although much remains to be determined,” they added.

Research has shown a lag of 10 to 20 years from exposure to a carcinogen to prostate cancer diagnosis. While WTC exposure was known to be linked to prostate cancer risk among responders, the length of time between exposure and cancer diagnosis was unknown.

Among the 54 394 rescue/recovery workers in the study, 1120 prostate cancer cases were diagnosed from 2002 to 2015.

The median time from the attacks to a diagnosis was 9.4 years, with the majority (66%) of cases diagnosed from 2009 to 2015.

Higher screening rates among first responders may have contributed to the increased incidence of prostate cancer seen in the study, the researchers acknowledged.

Comparing the responders who arrived earliest to the site with those who arrived later revealed a positive, monotonic, dose-response association with the early (2002-2006) and late (2007-2015) periods.

“The increased hazard among those who responded to the disaster earliest or were caught in the dust cloud suggests that a high intensity of exposure may have played some role in premature oncogenesis,” Hall and colleagues wrote. “Our findings support the need for continued research evaluating the burden of prostate cancer in WTC responders.”

Source: MedPage Today

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Common Chemical in Medical Products Linked to Breast Cancer

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Photo by Bill Oxford on Unsplash

Researchers in Japan have found that widely used chemicals called photoinitiators cause breast tumours to accelerate in mice. 

Photoinitiators, which release reactive molecules in response to UV radiation,  are used in a wide range of products, including plastics, paints, inks, and adhesives. Photoinitiators are present in common objects as well as in medical products and instruments such as dental fillers and containers.

Recent studies have demonstrated several health hazards associated with photoinitiators, raising safety concerns. In particular, the presence of these compounds in clinical instruments, routinely used for treating high-risk individuals such as cancer patients, has become a major cause for concern. Previous research has shown that three photoinitiators commonly found in plastics and paints 1-HCHPK, MBB, and MTMP show oestrogen-like effects on cultured breast cancer cells, increasing their proliferation. Found in marketed injection solutions, the clear link between oestrogen activity and breast cancer made determining their effect a priority.

In a study published in Current Research in Toxicology, lead researcher Dr Yoichi Kawasaki and Prof Toshiaki Sendo from Okayama University examined how exposure to 1-HCHPK, MBB, and MTMP affected the growth of transplanted breast cancer tumours in mice. They found that all three compounds caused a faster increase in the growth of breast tumors, within 13 weeks of treatment. “This study extends our previous findings and shows that in addition to promoting the proliferation of breast cancer cells in culture, these photoinitiators also increase the growth of breast tumours in live animals. This implies that they could also potentially hasten disease progression in breast cancer patients,” explained Dr Kawasaki.    

The study results show that 1-HCHPK, MBB, and MTMP have oestrogen-like activity and could thus act as hormonal disruptions. Given oestrogen’s role in regulating reproductive function in both men and women, such disruptions could affect not only patients with breast cancer, but also healthy individuals. While the researchers intend to explore the effects of photoinitiators on reproduction in future research, the present study informs breast cancer management, as well as making urgent call-to-action to eliminate toxic materials from medical equipment.

“Photoinitiators have helped us improve the quality of several commonly used products. But it is time we reconsider whether their benefits outweigh their risks, and our findings are an important milestone in encouraging this conversation. We hope that it will prompt more intensive research and stricter regulations on what materials can be adopted for commonly used products, especially those with medical applications,” said Dr Kawasaki.

Source: EurekAlert!

Categories : Cancer Ethics and LawTags :

Many Lung Cancer Patients Choose Euthanasia Without Exploring Treatment

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Photo by Adam Birkett on Unsplash

A Canadian study of lung cancer patients who opted for “medical assistance in dying” often proceeded without consultation with their radiation oncologist or medical oncologist.

In a Canadian study of 45 individuals diagnosed with lung cancer who used medical assistance in dying (also known as physician-assisted suicide), about 20% did not have a radiation oncologist involved when making the decision and 22% did not have a consultation with a medical oncologist, said Sara Moore, MD, of Ottawa Hospital Research Institute of the University of Ottawa.

Since 2016, about 60% of those seeking to end their life through legal means introduced in Canada had been diagnosed with cancer, Dr Moore explained in a presentation at the virtual World Conference on Lung Cancer.

Driven by loss of autonomy, control and dignity
The designated discussant, Monica Malec, MD, a geriatric and palliative care physician at the University of Chicago, said this was the first study to evaluate medical assistance in dying in patients with lung cancer, oncologists’ involvement, and treatment history.

“The demand for medical assistance in dying is increasing and is becoming more readily available to patients,” Dr Malec said. “Patients are seeking this option despite the availability of more effective and more tolerable treatment options. Existing literature suggests that loss of autonomy, control, and dignity are the primary drivers for seeking medical assistance in dying rather than uncontrolled symptoms, and the decision to pursue medical assistance in dying may occur pre-illness.”

Moore noted that while lung cancer accounts for 20%-25% of all cancer deaths overall, in the current study 17.5% of the patients had lung cancer diagnoses. “Lung cancer comprises slightly fewer medical assistance in dying cases than expected compared to lung cancer death rates,” she said.

Improved treatments disregarded
“Biomarker-driven targeted therapy and immunotherapy offer effective and tolerable new treatments, but a subset of patients undergo medical assistance in dying without accessing — or, in some cases, without being assessed for — these treatment options,” Dr Moore continued. “Most patients were assessed by an oncology specialist, though less than half received systemic therapy.”

“Given the growing number of efficacious and well-tolerated treatment options in lung cancer, consultation with an oncologist may be reasonable to consider for all patients with lung cancer who request medical assistance in dying,” she said.

The researchers screened data from the Ottawa region, and identified 256 patients with a cancer diagnosis who had used medical assistance in dying. Of these, 45 patients had a lung cancer diagnosis.About 85% had a history of tobacco smoking, and 36% were current smokers at the time they sought medical assistance in dying, Moore reported. Thirteen of these patients had no biopsy confirmation of their disease, but almost all (91%) opting for medical assistance in dying were diagnosed with metastatic disease. Average age was 72 years, and 64% (29 of 45 patients) were women, even though men are more often diagnosed with lung cancer, Dr Moore noted. 
Limitations included being limited to only a single region, and a lack of information on patients’ decision-making process.

Source: MedPage Today

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Bone Marrow Cell Mutations That Protect Against Cancers

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Source: NIH

People with shortened telomeres caused by rare disorders may be more likely to have blood cancers such as leukaemia or myelodyplastic syndrome (MS). Now researchers have discovered several “self-correcting” genetic mutations in bone marrow that may protect such patients from these cancers.

In a study published in the Journal of Clinical Investigation, these mutations can serve as biomarkers to indicate if patients with short telomere syndromes (STS) are likely to develop blood cancers.

“These are the most common cancers we see in patients with short telomere syndromes,” said Mary Armanios, MD, director of the Telomere Center and professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. “We know that at a certain point, the cells of patients with shortened telomeres either become cancerous or stay healthy.”

Dr Armanios and her team suspected that a self-correcting mechanism in areas of the body with high cell turnover, such as bone marrow, was allowing normal cells to turn malignant. Instead, it appears this mechanism protects against cells from becoming cancerous.

As over 300 billion blood cells are produced in the bone marrow daily, the researchers suspected they could find evidence of cellular self-correction in this area of the body, especially amid the spongey interior of bones, where quick adaptation is crucial for high-volume cell production.
The researchers tested the bone marrow and blood cells of 84 study participants divided into three groups: Those with STS and MS or leukaemia; those with short telomere syndromes and no MS or leukemia; and those in the control group without short telomere syndromes or any cancers.

Using ultra-deep genetic sequencing which picks up hard-to-detect mutations, Armanios and her team observed genetic mutations and self-correction in several telomere-associated genes. Nearly a quarter of patients with STS had these mutations, some even showing multiple mutations.

One such mutation in a gene called TERT enables the production of crucial parts of telomerase, which stabilises telomeres. By boosting telomerase production and overwriting faulty copies of the TERT gene, the researchers found that bone marrow cells seemed to self-correct to avoid becoming cancerous.

“Our findings speak to the versatility of the bone marrow and other areas with high cell turnover in the body,” says Armanios. “Such advantageous mutations provide the body with a better chance to protect itself. These findings may be important in the screening process of shortened telomere patients so that we can predict who may be protected from cancer.”

Source: John Hopkins Medicine

Categories : Cancer VaccinesTags :

HPV Vaccine to Cause Drop in Oropharyngeal Cancers

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Photo by Gustavo Fring at Pexels

Vaccinations against human papillomavirus (HPV), a major cause of oropharyngeal cancers, are expected to yield significant reductions in the rates of these cancers in the US after 2045, according to a new study.

The most common sexually transmitted infectious virus worldwide, HPV infection is often silent, and while most infections clear, some are chronic and can trigger cancers including mouth and throat (oropharyngeal), and cervical cancer as they disrupt DNA and inhibit tumour-suppressor proteins in infected cells. While there is no cure for existing HPV infections, vaccines can prevent new infections. The study appears online in JAMA Oncology.

“We estimate that most of the oropharyngeal cancers from 2018 to 2045 will occur among people who are 55 years and older and have not been vaccinated,” said study lead author Yuehan Zhang, a PhD candidate in the research group of Gypsyamber D’Souza, PhD, professor in the Department of Epidemiology at the Bloomberg School.

“HPV vaccination is going to work to prevent oropharyngeal cancers, but it will take time to see that impact, because these cancers mostly occur in middle age,” Prof D’Souza said.

Oropharyngeal cancer is the most common HPV-related cancer. Vaccination, though effective in prevention, has no effect against established HPV infections or against cells that have been transformed by HPV and are on their way to forming tumours, therefore recommended mainly for the young not yet exposed to sexually transmitted HPV. (People who were adults when the vaccine became available mostly did not receive it and remain at risk for these cancers)

In the new study, researchers at the Johns Hopkins Bloomberg School of Public Health analysed national databases on oropharyngeal cancer cases and HPV vaccinations, and projected the impact of HPV vaccination on the rates of these cancers in different age groups. They estimated that the oropharyngeal cancer rate would nearly halve between 2018 and 2045 among people ages 36–45. However, they also projected that the rate in the overall population would stay about the same from 2018-2045, due to still-rising rates of these cancers in older people, where most of these cancers occur.

The results suggest, though, that by 2045 HPV vaccination will have begun to make a significant impact. “Our projections suggest that by around 2033, nearly 100 cases of oropharyngeal cancer will be prevented each year, but by 2045 that figure will have increased by about ten times,” Zhang said.

Source: Johns Hopkins University Bloomberg School of Public Health

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Humans Still Beat AI in Breast Cancer Screening

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Source: National Cancer Institute

A review in The BMJ finds that humans still seem to beat AI when it comes to the accuracy of spotting possible cases of breast cancer during screening.

At this point, there is a lack of good quality evidence to support a policy of replacing human radiologists with artificial intelligence (AI) technology when screening for breast cancer, the researchers concluded.

A leading cause of death for among women the world over, mammography screening is a high volume, repetitive task for radiologists, and some cancers are not picked up.

Previous research has suggested that AI systems outperform humans and might soon be used instead of experienced radiologists. However, a recent review of 23 studies highlighted evidence gaps and concerns about the methods used.

To address this uncertainty, researchers reviewed 12 studies carried out since 2010. They found that, overall, the methods used in the studies were of poor quality, with low applicability to European or UK breast cancer screening programmes.

Three large studies involving nearly 80 000 women compared AI systems with the clinical decisions of the original radiologist. Of these, 1878 had screen detected cancer or interval cancer (cancer diagnosed in-between routine screening appointments) within 12 months of screening.

The majority (34 out of 36 or 94%) of AI systems in these three studies were less accurate than a single radiologist, and all were less accurate than the consensus of two or more radiologists, which is the standard practice in Europe.

In contrast, five smaller studies involving 1086 women reported that all of the AI systems evaluated were more accurate than a single radiologist. However, these were at high risk of bias and not replicated in larger studies.

In three studies, AI used as a pre-screen to triage which mammograms need to be examined by a radiologist and which do not screened out 53%, 45%, and 50% of women at low risk but also 10%, 4%, and 0% of cancers detected by radiologists.

The authors point to some study limitations such as excluding non-English studies, as well as the fast pace of AI development. Nevertheless, stringent study inclusion criteria along with rigorous and systematic evaluation of study quality suggests their conclusions are robust.

As such, the authors said: “Current evidence on the use of AI systems in breast cancer screening is a long way from having the quality and quantity required for its implementation into clinical practice.”

They added: “Well designed comparative test accuracy studies, randomized controlled trials, and cohort studies in large screening populations are needed which evaluate commercially available AI systems in combination with radiologists in clinical practice.”

Source: Medical Xpress

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Vulnerability Found in Solid Tumours

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Source: NCI

Researchers have found a weakness in a key enzyme key for solid tumour cancer cells’ ability to adapt and survive when oxygen levels are low.

The findings, published in Science Advances, will help researchers develop new treatment strategies to limit the progression of solid cancer tumours, which represent the majority of tumour types that arise in the body.

As tumours advance, the blood vessels that they previously relied on become unable to provide oxygen and nutrients to all parts of the tumour, which results in areas of hypoxia. Over time, this hypoxic environment leads to a buildup of acid inside the tumour cells.

To overcome this stress, the tumour cells adapt by releasing enzymes that neutralise the acidic conditions of their environment, enabling the cells to not only survive, but develop into a more aggressive form of tumour capable of spreading to other organs. One of these enzymes is called Carbonic Anhydrase IX (CAIX).

“Cancer cells depend on the CAIX enzyme to survive, which ultimately makes it their ‘Achilles heel.’ By inhibiting its activity, we can effectively stop the cells from growing,” explained senior author Dr Shoukat Dedhar, professor in UBC faculty of medicine’s department of biochemistry and molecular biology and distinguished scientist at BC Cancer.

Previously, Dr Dedhar and colleagues had identified a unique compound, known as SLC-0111 (which is currently being evaluated in Phase 1 clinical trials) as a powerful CAIX enzyme inhibitor. Though the effectiveness of this compound in suppressing tumour growth and spread has been tested in pre-clinical models, other cellular properties diminish its effectiveness.

In this study, the researchers set out to investiagete these cellular properties and identify other weaknesses of the CAIX enzyme with the help of a powerful tool known as a genome-wide synthetic lethal screen. This tool systematically deletes one gene at a time from a cancer cell’s genome to determine if a cancer cell can be killed by eliminating the CAIX enzyme together with another specific gene.

According to Dr Dedhar, they had surprising results and point to an unexpected role of proteins and processes that control a form of cell death called ferroptosis, a form of cell death that occurs from an iron build up which weakens the tumour’s metabolism and cell membranes.

“We now know that the CAIX enzyme blocks cancer cells from dying as a result of ferroptosis,” said Dr Dedhar. “Combining inhibitors of CAIX, including SLC-0111, with compounds known to bring about ferroptosis results in catastrophic cell death and debilitates tumour growth.”

The development of drugs to induce ferroptosis is underway around the world, and this study is contributing to their work.

Source: University of British Columbia

Categories : Cancer PaediatricsTags :

Existing Drug Could Target Childhood Leukaemia

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Existing Drug Could Target Childhood Leukaemia

A new study published in PNAS has shown that the tumour-inhibiting gene TET2 is silenced in a large fraction of cases of acute lymphoblastic leukaemia (ALL) in children. The scientists show that the gene can be reactivated by an existing drug, 5-azacytidine, suggesting that it could be used a as targeted therapy for ALL in children.

“T-cell acute lymphoblastic leukaemia (T-ALL) is a devastating disease for the affected children and their families. One of five children affected do not survive the disease. The ultimate goal of my research is to ensure that all children can be cured. Our discovery may pave the way for clinical studies of 5-azacytidine as a new therapy for this poorly understood disease. The more treatment options we have for T-ALL the more chance we have of beating this aggressive cancer,” explained study leader Colm Nestor, senior lecturer in the Department of Biomedical and Clinical Sciences .

One of the characteristics of cancer cells is that they lose their cellular identity. One of the reasons for this is certain genes being silenced while others are activated. Switching genes on and off is controlled by epigenetic modification, where small chemical groups are attached to and removed from DNA, such as DNA methylation. The pattern of DNA-methylation is often altered in cancer cells, making them attractive targets for cancer drug research.

In the recently published study, the researchers were interested in an enzyme, TET2, that removes methyl groups from DNA. The gene that codes for TET2 is often affected by mutations in adult leukaemias. In children however, harmful mutations in TET2 are very rare, which led the researchers to speculate whether TET2 function is affected differently in child leukaemias. They analysed the gene expression patterns in cancer cells from more than 300 patients with T-ALL, and found that in many cases the TET2 gene was silenced.

It turned out that  methylation often silenced the TET2 gene. The scientists therefore decided to treat tumour cells in culture with a drug, 5-azacytidine, that removes methyl groups from DNA. This drug is used to treat certain leukaemias in adults.

“We found that one type of T-ALL cell, whose DNA seems to be highly methylated, is more sensitive to azacytidine than other cells that are not highly methylated. The drug actually turns silenced TET2 back on by demethylating it, so this might be a targeted therapy for a subset of cases. We suggest that azacytidine may have a doubled effect in these cells, since both the drug itself and TET2 kill cancer cells by demethylating the genome,” explained Colm Nestor.

Since 5-azacytidine is an approved drug, the researchers hope that it will be a much quicker path to treatment than when developing a novel drug.

“Chemotherapy agents have a broad effect and can be used for many patients, but they also kill healthy cells and can give rise to serious undesired effects. Targeted treatment, on the other hand, only works for a small fraction of patients, but is extremely specific. We need an arsenal of drugs to use for patients who experience relapses, and for those whose cancer does not respond to chemotherapy,” said Colm Nestor.

The researchers will continue with experiments to determine the effects of activating TET2 in these cancer cells, and to see if 5-azacytidine can function as targeted therapy in other types of cancer.

“The fact that we can target the loss of TET2 using the drug 5-azacytidine makes me hopeful that this treatment can help T-ALL patients in the future,” said researcher Maike Bensberg, PhD student at Linköping University.

Source: Linköping University

Categories : Cancer PaediatricsTags :

A Brief Window of Opportunity to Halt Certain Paediatric Gliomas

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Photo by Jeffrey Riley on Unsplash

In a pre-clinical study, investigators identified a vulnerability in a developmental signaling pathway that can be hijacked to drive paediatric low-grade glioma (pLGG) formation.

The study, published in Developmental Cell, demonstrated that targeted treatment prevents tumor formation, long before irreversible damage to the optic nerve can cause permanent loss of vision. This finding will inform chemo-prevention therapeutic trials in the future.

Brain tumours are the most common solid tumours in children, the most prevalent of which are pLGGs, of which 10 to 15% arise in patients with the familial cancer predisposition syndrome known as neurofibromatosis type 1 (NF1). Thi increases risks of developing tumours along the nerves and in the brain.

Almost 20% of children with NF1 develop pLGGs along the optic pathway, also known as NF1-associated optic pathway glioma (NF1-OPG). Despite many advances in cancer therapy, there are no definitive therapies available that prevent or alleviate the neurological deficits (i.e. vision loss) and that could improve the quality of life.

“The evidence presented can inform chemoprevention therapeutic trials for children with NF1-OPG. This therapeutic strategy may also be applicable to children with the developmental disorders that are at high risk of developing pediatric tumors, such as other RASopathies,” said Yuan Zhu, PhD, scientific director and Gilbert Family Endowed professor at the Gilbert Family Neurofibromatosis Institute and associate director of the Center for Cancer and Immunology Research.

The mechanism of vulnerability to pLGGs during development is not fully understood. It could be that the cell population of origin for this debilitating tumour is transiently proliferative during development. The NF1 gene produces a protein that inhibits MEK/ERK signalling, thereby helping regulate normal cell proliferation, survival and differentiation. With loss of NF1 function, it abnormally activates the MEK/ERK signalling pathway, leading to tumour formation.

Certain transient cells present during development of the brain and optic nerve are vulnerable to tumour formation because they depend on MEK/ERK signalling. Researchers identified cells dependent on the pathway and grew during a transient developmental window as the lineage-of-origin for NF1-OPG in the optic nerve. They then used a genetically engineered pre-clinical model to design a transient, low-dose chemo-preventative strategy, which prevented these tumours entirely.

“When we provided a dose-dependent inhibition of MEK/ERK signaling, it rescued the emergence and increase of brain lipid binding protein-expressing (BLBP+) migrating GPs glial progenitors, preventing NF1-OPG formation,” the researchers wrote. “Equally importantly, the degree of ERK inhibition required for preventing NF1-OPG formation also greatly improved the health and survival of the NF1-deficient model.”

Clinical trials using MEK inhibitors (MEKi) are underway for children as young as 1 month old, making the design of a chemo-preventative trial using a MEKi to treat children with NF1 more feasible. This treatment approach might not only prevent OPG formation, but also other NF1-associated and RASopathies-associated developmental defects and tumours.

Source: Children’s National Hospital