Tag: cancer

Plant Virus-based Treatment Protects Against Lung Tumours

Image source: CDC/Unsplash

Using a virus that grows in black-eyed pea plants, nanoengineers developed a new treatment that could keep metastatic cancers at bay from the lungs. 

Not only did the treatment slow tumour growth in the lungs of mice with either metastatic breast cancer or melanoma, it also prevented or drastically minimised the spread of these cancers to the lungs of healthy mice that were challenged with the disease. The research was published in Advanced Science.

Researchers developed an experimental treatment that combats metastatic spread. This involves a plant virus called the cowpea mosaic virus, harmless to animals and humans, but which the body still registers as a foreign invader, thus triggering an immune response that could also boost the body’s cancer-fighting ability.

The idea is to use the plant virus to help the body’s immune system recognise and destroy cancer cells in the lungs. The virus itself is not infectious in our bodies, but it has all these danger signals that alarm immune cells to go into attack mode and search for a pathogen, said Nicole Steinmetz, professor of nanoengineering at the University of California San Diego.

To draw this immune response to lung tumours, Prof Steinmetz’s lab engineered nanoparticles made from the cowpea mosaic virus to target a protein in the lungs. The protein, called S100A9, is expressed and secreted by immune cells that help fight infection in the lungs. Overexpression of S100A9 has been observed to play a role in tumour growth and spread.

“For our immunotherapy to work in the setting of lung metastasis, we need to target our nanoparticles to the lung,” said Prof Steinmetz. “Therefore, we created these plant virus nanoparticles to home in on the lungs by making use of S100A9 as the target protein. Within the lung, the nanoparticles recruit immune cells so that the tumors don’t take.”

“Because these nanoparticles tend to localise in the lungs, they can change the tumor microenvironment there to become more adept at fighting off cancer — not just established tumors, but future tumors as well,” said Eric Chung, a bioengineering PhD student in Steinmetz’s lab who is one of the co-first authors on the paper.

To make the nanoparticles, the researchers infected black-eyed pea plants with cowpea mosaic virus, and harvested the virus in the form of ball-shaped nanoparticles. They then fixed S100A9-targeting molecules to the particles’ surfaces.

The researchers performed both prevention and treatment studies. In the prevention studies, they first injected the plant virus nanoparticles into the bloodstreams of healthy mice, and then later injected either triple negative breast cancer or melanoma cells into these mice. Treated mice showed a dramatic reduction in the cancers spreading to their lungs compared to untreated mice.

In the treatment studies, the researchers administered the nanoparticles to mice with metastatic tumours in their lungs. The treated mice exhibited smaller lung tumours and survived longer than untreated mice.

Prof Steinmetz envisions that the treatment could be useful after tumourectomy. “It wouldn’t be meant as an injection that’s given to everyone to prevent lung tumours. Rather, it would be given to patients who are at high risk of their tumors growing back as a metastatic disease, which often manifests in the lung. This would offer their lungs protection against cancer metastasis,” she said.

More detailed immunotoxicity and pharmacology studies are needed before this can progress to a treatment. Future studies will also explore combining this with standard cancer therapies such as chemotherapy.

Source: University of California – San Diego

Childhood Cancer Survivor Set to Break Barriers in Space

Hayley Arcenaux, seated furthest left, is the Medical Officer for the Inspiration4 flight. She is a survivor of childhood cancer and works as a physician assistant at St Jude’s Children’s Hospital, for which the flight is raising funds and awareness.

The first chartered spaceflight into orbit, scheduled for launch on September 15, will have a crewmember who is both a childhood cancer survivor and physician assistant as part of the crew. 

The three-day long mission aboard a SpaceX Dragon spacecraft was chartered by entrepreneur Jared Isaacman. Dubbed Inspiration4, the flight is in fact also raising money and awareness for St Jude Children’s Hospital, which was given two of the four seats on the spacecraft. The funds raised for the hospital are believed to have exceeded the cost of the flight.

Isaacman offered the first seat to 29 year-old Hayley Arceneux, who works as a physician assistant at St Jude’s and will be the medical officer for the flight. She was also a patient at the very same hospital. At age 10, she was diagnosed with osteosarcoma, the most common primary paediatric bone malignancy. In addition to a dozen rounds of chemotherapy, she had a limb-sparing operation which replaced her knee and inserted a titanium reinforcing rod in her femur. This will make her the first person with a prosthetic in space. Such a medical history would have immediately disqualified her for astronaut selection with any of the government-run space agencies like NASA.

In an interview with The Cut, she described her work as a physician assistant at St Jude’s: “I work inpatient… with leukaemia and lymphoma patients specifically. The majority of them received their cancer diagnoses pretty recently, so a big part of  my role is helping to educate and support families through the beginning of treatment. I help them understand, What is cancer? What does the treatment process look like? What should I expect?

“We also manage the kids while they are in treatment. If they get an infection or if they get a fever, we take that really seriously. So I’ll manage their IV antibiotics or other treatment-related complications that can occur.. I check on patients, assess labs, order tests, update families on the results, order meds for outpatients. It is a lot of coordinating and educating. It’s hard, but it’s the greatest job in the world.”

St Jude’s held an auction for the other crew seat that Isaacman offered. The winning bidder declined the seat and gifted it to data engineer Christopher Sembroski. The final seat was won in an entrepreneurial competition by Dr Sian Proctor, a geologist and pilot who narrowly missed out on being chosen as a NASA astronaut. 

Speaking about the auction, Richard C. Shadyac Jr, president and chief executive of American Lebanese Syrian Associated Charities, which raised fund for St Jude’s, said: “The impact of the Inspiration4 mission has been immeasurable, serving as an incredible platform to educate and engage millions in the movement to find cures and deliver care for childhood cancer and other catastrophic diseases through accelerated research and treatment. The auction is a critical component of the overall campaign as it enables us to reach new audiences and supporters as we work to fulfill our mission.”

So far, $100 million has been raised for St Jude’s.

While in space, the crew will conduct experiments such as examining fluid shifts in zero gravity using ultrasound, as well as other medical experiments including measuring blood glucose levels — in order to help expand space travel to those with diabetes.

A documentary has been made of the crew’s training, and is available to stream on Netflix.

Less than Half of Community Oncologists Use Biomarker Testing

Photo by Robina Weermeijer on Unsplash

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

Elevated Cancer Risk in 9/11 Responders 20 Years On

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

Existing Drug Could Target Childhood Leukaemia

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

A Brief Window of Opportunity to Halt Certain Paediatric Gliomas

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

Cancer Surgery Patients Have a Reduced Hospital Stay with ‘Prehabilitation’

Photo by Martha Dominguez de Gouveia on Unsplash

A new approach to improve their fitness for surgery reduced the length of hospital stay for cancer patients, according to a new study.

Termed ‘prehabilitation’, the study’s approach includes exercise, nutrition and psychological and social interventions to bolster physical and mental health before surgery.

The study, published in the Annals of Surgery, found that prehabilitation interventions of between one and four weeks reduced cancer patients’ stay in hospital by 1.8 days compared with usual care.

Study author Dr Chris Gaffney from Lancaster Medical School said: “Surgery is like a marathon in terms of stressing the body, and you wouldn’t run a marathon without training.”

The researchers found that as little as one week can still benefit patient outcomes, indicating that prehabilitation should be recommended to accelerate recovery from cancer surgery, as shown by a reduced hospital length of stay.

Study author Dr Joel Lambert, now a postgraduate student at Lancaster Medical School and a surgeon at East Lancashire Teaching Hospitals NHS Trust, said: “We think that it may also confer a survival advantage for cancer patients as they can get to follow up treatments like chemotherapy more quickly.

“We think that the patient groups most likely to benefit are the ones with lower levels of fitness at baseline. In the Northwest we have some of the most socioeconomically deprived populations in the UK. This subset tend to have more co-morbid conditions hence less fit.”  

The patients studied were those with liver, colorectal, and upper gastrointestinal cancer, and who are often less fit than other cancer patients.

The study interventions were grouped into three types

  • Multimodal prehabilitation: exercise, which included both nutrition and psychosocial support,
  • Bimodal prehabilitation: exercise and nutrition or psychosocial support
  • Unimodal prehabilitation: exercise or nutrition alone

The exercise interventions included aerobic, resistance, and both aerobic and resistance exercises at all levels of intensity, some supervised by a kinesiologist or physiotherapist, while others were home-based exercise regimes. These ranged from one to four weeks and all interventions were within the current NHS surgery targets for cancer surgery.

The researchers concluded: “Future studies should focus on identifying patients who would benefit most from prehabilitation and the mechanistic underpinning of any improvement in clinical outcomes. Studies should closely monitor nutrition intake to determine if the response to exercise prehabilitation is dependent upon nutritional status. Lastly, mortality should be monitored for 12 months post surgery to determine if prehabilitation has any effect beyond 30 or 90 days.”

Source: Lancaster University

How do Patients Who Exit Clinical Trials Early Feel?

Source: JD Mason on Unsplash

A new study has helped researchers understand the experiences of people who withdraw from clinical cancer trials.

Cancer clinical trials (CCTs) provide patients with an opportunity to receive experimental drugs, tests, and/or procedures that may lead to remissions. Such opportunities can be a great benefit for those who took part, but there is little known of the experiences of participants who withdraw from CCTs.

To address this, a first-of-its-kind study from the University of Pennsylvania School of Nursing (Penn Nursing) was conducted to better understand the post-trial needs of these patients and define responsible transitions when patients exit CCTs.

“Understanding the post-trial needs of patients with cancer and their families represents a measure of ethical respect of the many contributions that patients with cancer make to advancing our scientific knowledge and finding treatments that save lives,” said the study’s lead researcher, Connie M Ulrich, the Lillian S Brunner Chair in Medical and Surgical Nursing, professor of nursing, professor of medical ethics and health policy.

The study revealed three important areas:

  • Patients exiting CCTs feel intense symptoms, emotions, and awareness that their life spans are short and options seem limited.
  • The limited discussions with patients who are exiting on their immediate post-trial care needs can result in many feeling that there is no clear path forward.
  • Good communication that deliberately includes attention to post-trial needs throughout the CCT is needed to help scared and disappointed patients navigate their next steps.

The study is set for publication on the JAMA Network.

Source: University of Pennsylvania

Host Genes Can Hinder H. Pylori Eradication

Helicobacter pylori is a strong risk factor for gastric cancer and other gastrointestinal disorders, and efforts to eradicate it using a combination of antibiotics and proton pump inhibitors (PPIs) often fail.

A new study has linked this eradication failure with genetic variations that increase the activity of the CYP2C19 enzyme, which metabolises first-generation PPIs.

These so-called ‘fast metabolisers’ may prevent PPIs from suppressing gastric acid production, which is necessary for successful H. pylori eradication.

Analysing 57 studies from 11 countries, the researchers found that the failure rate of H. pylori eradication more than doubled in people with a version of the CYP2C19 gene that increased its metabolic activity. Their results were published in Gastroenterology.

However, CYP2C19 variants were not linked to eradication failure if the fast metabolisers were treated with newer PPIs such as esomeprazole and rabeprazole, which are less metabolised by the enzyme or which bypass CYP2C19 metabolism.

Further well-designed studies are needed to determine whether eradication rates could be improved with higher or more frequent dosages of first-generation PPIs to people with the fast metaboliser gene variant, noted the paper’s corresponding author, Shailja Shah, MD, MPH.
“Even small improvements in H. pylori eradication rates would likely translate to substantial collateral health, economic and societal benefits,” the researchers concluded.

Source: Vanderbilt University

Cancer Survivors Experience Accelerated Ageing

Source: JD Mason on Unsplash

A new study published in Journal of the American Geriatrics Society indicates that cancer survivors, especially older ones, are more likely to experience faster functional decline as they age, compared with those without a history of cancer.

For the study, 1728 men and women (aged 22 to 100 years) were evaluated from 2006 to 2019, with 359 of these adults reporting a history of cancer. Among all participants, a history of cancer was associated with a 1.42 greater odds of weak grip strength. Those with a history of cancer and over 65 had a 1.61 greater odds of slow gait speed than those with no cancer history, and also had lower physical performance scores. Additionally, compared with those with no history of cancer, older individuals with a history of cancer experienced steeper declines in grip strength and gait speed. Reduced prefrontal cortex area is one of the factors thought to contribute to slow gait.

“Findings from our study add to the evidence that cancer and its treatment may have adverse effects on aging-related processes, putting cancer survivors at risk for accelerated functional decline,” said senior author Lisa Gallicchio, PhD, of the National Cancer Institute. “Understanding which cancer survivors are at highest risk, and when the accelerated decline in physical functioning is most likely to begin, is important in developing interventions to prevent, mitigate, or reverse the adverse aging-related effects of cancer and its treatment.”

Source: EurekAlert!