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"Dark Matter" That Shapes Cancer Behavior Unveiled in Landmark Studies – Technology Networks

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Cancers can evolve to become more aggressive without relying only on DNA mutations, two major studies published simultaneously in Nature reveal.

The research characterizes a whole extra level of control of cancer gene activity within tumours, which the researchers describe as cancer’s “dark matter”.

The two landmark studies showed how a level of gene control called ‘epigenetics’ plays a central role in the development and progression of bowel cancer. Testing cancers for DNA mutations alone misses this level of control – and so can fail to predict how cancers may behave and respond to treatment.

The research, published today in Nature, was led by scientists at The Institute of Cancer Research, London, Human Technopole in Milan and Queen Mary University of London. It was funded by Wellcome, the Medical Research Council (MRC) and Cancer Research UK.

More accurately predict cancer’s behaviour

The research could change the way we think about cancer and its treatment – and lead to new forms of tests that predict cancer’s behaviour more accurately.

Epigenetics involves chemical changes to the three-dimensional structure of DNA which don’t alter the DNA code itself but can control access to genes. It has increasingly been recognised as playing an important role in the development of cancer.

Now for the first time, scientists have been able to track the influence of epigenetic control on how bowel cancers grow, develop and evolve over time, separately from the influence of mutations to the DNA code, which they mapped simultaneously.

The researchers observed important epigenetic changes in every cancer they examined and found signs that epigenetic changes are involved in cancer’s ability to evolve and become more aggressive.

In the first paper, the researchers collected 1,373 samples from 30 bowel cancers and looked at epigenetic changes as cancers evolved. They showed that epigenetic changes:

  • are highly common in cells which have become cancerous and occur around genes already known to drive cancer
  • are heritable, meaning they can be inherited by cells with each cell division, and that they contribute to cancer evolution
  • influence how cancer cells accumulate DNA mutations
  • were present in cancer cells that had survival advantages which helped them to grow more than other cells.

Survival advantages

The second Nature paper aimed to understand why cancer cells within the same tumour can be so different to one another – a characteristic that helps some cells develop survival advantages and become resistant to cancer treatments.

The researchers wanted to understand whether the diversity of cell types within a tumour is governed by variation in the DNA code, or something else. They looked at the DNA sequence in diverse samples taken from different parts of the same tumour.

They found:

  • less than 2 per cent of changes in the DNA code in independent areas of a tumour were associated with changes in gene activity
  • variation in cancer cell characteristics throughout tumours is often governed by factors other than DNA mutations.

The researchers point out that their findings are observational in nature and more work needs to be done to determine cause and effect between specific epigenetic changes and modifications to cancer behaviour.

Fundamental advance in our understanding of cancer

Collectively, the papers represent a fundamental advance in our understanding of cancer. The researchers stress that DNA mutations are fundamental in “setting the scene” for a cancer’s development and evolution – but that much of the subsequent behaviour of cancer cells is determined by other factors, such as epigenetics.

That could help explain why DNA tests don’t always predict how cancers will respond to treatment and help doctors to tailor treatments for patients more effectively. It could also explain why some environmental exposures can cause cancer without leading to mutations in the DNA code.

Professor Trevor Graham, Director of the Centre for Evolution and Cancer at the ICR, said:

“We’ve unveiled an extra level of control for how cancers behave – something we liken to cancer’s ‘dark matter’. For years our understanding of cancer has focused on genetic mutations which permanently change the DNA code. But our research has shown that the way the DNA folds up can change which genes are read without altering the DNA code and this can be very important in determining how cancers behave.

“I hope our work will change the way we think about cancer and its treatment – and should ultimately affect the way patients are treated. Genetic testing for cancer mutations only gives us part of the picture about a person’s cancer – and is blind to ‘epigenetic’ changes to how genes are read. By testing for both genetic and epigenetic changes, we could, potentially, much more accurately predict which treatments will work best for a particular person’s cancer.”

Professor Andrea Sottoriva, Head of the Computational Biology Research Centre at Human Technopole in Milan, who co-led the research, said:

“When we study how cancers evolve over time, we tend to look at DNA mutations, but it’s clear that epigenetic changes also enable cancer to adapt and develop a survival advantage over other cells.

“We have for the first time been able to map epigenetic changes alongside the accumulation of DNA mutations as a colorectal tumour evolves. This provides exciting opportunities to create new treatments for cancer that don’t target the effects of DNA mutations, but instead the epigenetic changes which determine how genes are read.”

“Open’s up exciting future opportunities”

Professor Kristian Helin, Chief Executive of the ICR, London, and a world leader in the study of epigenetics, said:

“This discovery represents an exciting advance in our understanding of cancer biology.  Cancer’s ability to rapidly change and evolve is a key reason why it is so hard to treat. Exactly how cancer cells do this, and the factors that control how it can adapt to evade treatment, is not well understood.

“This important work demonstrates the potential role of epigenetic regulation in the development of cancer and the complexity of its behaviour. It opens exciting future opportunities to assess cancer using both genetic and epigenetic tests, and eventually to treat cancer with epigenetic-directed drugs.”

References:

  1. Heide T, Househam J, Cresswell GD, et al. The co-evolution of the genome and epigenome in colorectal cancer. Nature. 2022:1-11. doi: 10.1038/s41586-022-05202-1 
  2. Househam J, Heide T, Cresswell GD, et al. Phenotypic plasticity and genetic control in colorectal cancer evolution. Nature. 2022:1-10. doi: 10.1038/s41586-022-05311-x

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Older patients, non-English speakers more likely to be harmed in hospital: report

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Patients who are older, don’t speak English, and don’t have a high school education are more likely to experience harm during a hospital stay in Canada, according to new research.

The Canadian Institute for Health Information measured preventableharmful events from 2023 to 2024, such as bed sores and medication errors,experienced by patients who received acute care in hospital.

The research published Thursday shows patients who don’t speak English or French are 30 per cent more likely to experience harm. Patients without a high school education are 20 per cent more likely to endure harm compared to those with higher education levels.

The report also found that patients 85 and older are five times more likely to experience harm during a hospital stay compared to those under 20.

“The goal of this report is to get folks thinking about equity as being a key dimension of the patient safety effort within a hospital,” says Dana Riley, an author of the report and a program lead on CIHI’s population health team.

When a health-care provider and a patient don’t speak the same language, that can result in the administration of a wrong test or procedure, research shows. Similarly, Riley says a lower level of education is associated with a lower level of health literacy, which can result in increased vulnerability to communication errors.

“It’s fairly costly to the patient and it’s costly to the system,” says Riley, noting the average hospital stay for a patient who experiences harm is four times more expensive than the cost of a hospital stay without a harmful event – $42,558 compared to $9,072.

“I think there are a variety of different reasons why we might start to think about patient safety, think about equity, as key interconnected dimensions of health-care quality,” says Riley.

The analysis doesn’t include data on racialized patients because Riley says pan-Canadian data was not available for their research. Data from Quebec and some mental health patients was also excluded due to differences in data collection.

Efforts to reduce patient injuries at one Ontario hospital network appears to have resulted in less harm. Patient falls at Mackenzie Health causing injury are down 40 per cent, pressure injuries have decreased 51 per cent, and central line-associated bloodstream infections, such as IV therapy, have been reduced 34 per cent.

The hospital created a “zero harm” plan in 2019 to reduce errors after a hospital survey revealed low safety scores. They integrated principles used in aviation and nuclear industries, which prioritize safety in complex high-risk environments.

“The premise is first driven by a cultural shift where people feel comfortable actually calling out these events,” says Mackenzie Health President and Chief Executive Officer Altaf Stationwala.

They introduced harm reduction training and daily meetings to discuss risks in the hospital. Mackenzie partnered with virtual interpreters that speak 240 languages and understand medical jargon. Geriatric care nurses serve the nearly 70 per cent of patients over the age of 75, and staff are encouraged to communicate as frequently as possible, and in plain language, says Stationwala.

“What we do in health care is we take control away from patients and families, and what we know is we need to empower patients and families and that ultimately results in better health care.”

This report by The Canadian Press was first published Oct. 17, 2024.

Canadian Press health coverage receives support through a partnership with the Canadian Medical Association. CP is solely responsible for this content.

The Canadian Press. All rights reserved.

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Alberta to launch new primary care agency by next month in health overhaul

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CALGARY – Alberta’s health minister says a new agency responsible for primary health care should be up and running by next month.

Adriana LaGrange says Primary Care Alberta will work to improve Albertans’ access to primary care providers like family doctors or nurse practitioners, create new models of primary care and increase access to after-hours care through virtual means.

Her announcement comes as the provincial government continues to divide Alberta Health Services into four new agencies.

LaGrange says Alberta Health Services hasn’t been able to focus on primary health care, and has been missing system oversight.

The Alberta government’s dismantling of the health agency is expected to include two more organizations responsible for hospital care and continuing care.

Another new agency, Recovery Alberta, recently took over the mental health and addictions portfolio of Alberta Health Services.

This report by The Canadian Press was first published Oct. 15, 2024.

The Canadian Press. All rights reserved.

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Experts urge streamlined, more compassionate miscarriage care in Canada

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Rana Van Tuyl was about 12 weeks pregnant when she got devastating news at her ultrasound appointment in December 2020.

Her fetus’s heartbeat had stopped.

“We were both shattered,” says Van Tuyl, who lives in Nanaimo, B.C., with her partner. Her doctor said she could surgically or medically pass the pregnancy and she chose the medical option, a combination of two drugs taken at home.

“That was the last I heard from our maternity physician, with no further followup,” she says.

But complications followed. She bled for a month and required a surgical procedure to remove pregnancy tissue her body had retained.

Looking back, Van Tuyl says she wishes she had followup care and mental health support as the couple grieved.

Her story is not an anomaly. Miscarriages affect one in five pregnancies in Canada, yet there is often a disconnect between the medical view of early pregnancy loss as something that is easily managed and the reality of the patients’ own traumatizing experiences, according to a paper published Tuesday in the Canadian Medical Association Journal.

An accompanying editorial says it’s time to invest in early pregnancy assessment clinics that can provide proper care during and after a miscarriage, which can have devastating effects.

The editorial and a review of medical literature on early pregnancy loss say patients seeking help in emergency departments often receive “suboptimal” care. Non-critical miscarriage cases drop to the bottom of the triage list, resulting in longer wait times that make patients feel like they are “wasting” health-care providers’ time. Many of those patients are discharged without a followup plan, the editorial says.

But not all miscarriages need to be treated in the emergency room, says Dr. Modupe Tunde-Byass, one of the authors of the literature review and an obstetrician/gynecologist at Toronto’s North York General Hospital.

She says patients should be referred to early pregnancy assessment clinics, which provide compassionate care that accounts for the psychological impact of pregnancy loss – including grief, guilt, anxiety and post-traumatic stress.

But while North York General Hospital and a patchwork of other health-care providers in the country have clinics dedicated to miscarriage care, Tunde-Byass says that’s not widely adopted – and it should be.

She’s been thinking about this gap in the Canadian health-care system for a long time, ever since her medical training almost four decades ago in the United Kingdom, where she says early pregnancy assessment centres are common.

“One of the things that we did at North York was to have a clinic to provide care for our patients, and also to try to bridge that gap,” says Tunde-Byass.

Provincial agency Health Quality Ontario acknowledged in 2019 the need for these services in a list of ways to better manage early pregnancy complications and loss.

“Five years on, little if any progress has been made toward achieving this goal,” Dr. Catherine Varner, an emergency physician, wrote in the CMAJ editorial. “Early pregnancy assessment services remain a pipe dream for many, especially in rural Canada.”

The quality standard released in Ontario did, however, prompt a registered nurse to apply for funding to open an early pregnancy assessment clinic at St. Joseph’s Healthcare Hamilton in 2021.

Jessica Desjardins says that after taking patient referrals from the hospital’s emergency room, the team quickly realized that they would need a bigger space and more people to provide care. The clinic now operates five days a week.

“We’ve been often hearing from our patients that early pregnancy loss and experiencing early pregnancy complications is a really confusing, overwhelming, isolating time for them, and (it) often felt really difficult to know where to go for care and where to get comprehensive, well-rounded care,” she says.

At the Hamilton clinic, Desjardins says patients are brought into a quiet area to talk and make decisions with providers – “not only (from) a physical perspective, but also keeping in mind the psychosocial piece that comes along with loss and the grief that’s a piece of that.”

Ashley Hilliard says attending an early pregnancy assessment clinic at The Ottawa Hospital was the “best case scenario” after the worst case scenario.

In 2020, she was about eight weeks pregnant when her fetus died and she hemorrhaged after taking medication to pass the pregnancy at home.

Shortly after Hilliard was rushed to the emergency room, she was assigned an OB-GYN at an early pregnancy assessment clinic who directed and monitored her care, calling her with blood test results and sending her for ultrasounds when bleeding and cramping persisted.

“That was super helpful to have somebody to go through just that, somebody who does this all the time,” says Hilliard.

“It was really validating.”

This report by The Canadian Press was first published Oct. 15, 2024.

Canadian Press health coverage receives support through a partnership with the Canadian Medical Association. CP is solely responsible for this content.

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