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Research uncovers how breast cancer cells “hibernate” to avoid treatment
Researchers have identified a key mechanism used by cancer cells to evade therapy by remaining in a dormant state
Scientists have discovered how breast cancer cells can “hibernate” to avoid treatment and “wake up” years later, causing a relapse that is more difficult to treat.
The research, published in the journal Cancer Discovery, has revealed the role of “epigenetics” in controlling how cancer cells can become dormant and suggested a strategy to target it before the cells “wake up”.
Epigenetic changes alter how your body reads your DNA, without changing the DNA code itself.
Patients with oestrogen receptor positive (ER+) breast cancer – which make up 80 per cent of all breast cancers – have a continued risk of their cancer recurring for many years or even decades after their original diagnosis and surgery. To reduce their risk of relapse, patients undergo five to ten years of hormone therapy to target any remaining cancer cells.
The team at The Institute of Cancer Research, London, found that this hormone therapy could, in some cases, play a role in triggering epigenetic changes that alter the state of some breast cancer cells, causing them to become dormant and evade treatment.
The researchers discovered that specific changes in key epigenetic regulators that control gene transcription, including the modification of histone H3 at lysine 9 (H3K9me2), were responsible for this dormant state. These changes remain until the cell “wakes up” and begins dividing rapidly again.
The scientists found that blocking these regulators – by inhibiting the enzymes that catalyse them – prevented the cells from becoming dormant, and killed the cancer cells that were already dormant. They also discovered that in people with low expression of these enzymes, their cancer had a lower risk of coming back years later.
The team studied ER+ breast cancer cells that they tagged with unique barcodes, an innovative way to study millions of cells through space and time. They mimicked hormone therapy treatment on the cells and saw that while most cells died, others became dormant and stopped proliferating.
Using mass spectrometry, the researchers discovered that hormone therapy treatment triggered changes to histone modifications, including H3K9me2, as the cells went into dormancy.
Histone modifications are chemical tags that are added to or removed from DNA, or the proteins DNA is wrapped around. Epigenetic modifications such as this are chemical changes to the three-dimensional structure of DNA, which do not alter the DNA code itself but can control access to genes.
The researchers set out to uncover whether blocking these epigenetic changes could prevent the cells from becoming dormant and evading treatment. To do this, they inhibited the enzyme G9a, which catalyses H3K9me2.
The researchers first tested this on cells which had just been treated with hormone therapy and found that it prevented the cancer cells from entering dormancy – in fact, it killed the cells.
Then, they tested it on cells which were already in a dormant state and found that inhibiting G9a killed dormant cancer cells.
To understand the importance of G9a in people, the researchers studied a cohort of patients with ER+ breast cancer. They found that for those who had low expression of enzymes such as G9a, their breast cancer had a significantly lower risk of relapse over the course of 15 to 20 years.
Professor Luca Magnani, professor of epigenetic plasticity at The Institute of Cancer Research, said: “After surgery to remove primary oestrogen receptor positive breast cancer, patients are given five to ten years of hormone therapy which aims to kill any remaining cancer cells.
“We know that this doesn’t work for all patients though, as their breast cancer can return years, or even decades later. We wanted to better understand why breast cancer does return so we can hopefully find ways to stop it – so people don’t have to live in fear or face the devastating news of a relapse.
“Our research identified a key mechanism used by cancer cells to evade therapy by remaining in a dormant state, hibernating before they ‘wake up’ years later and begin to rapidly divide again.
“I hope our early findings will next lead to research to target these dormant breast cancer cells so that one day, without the need for years of hormone therapy, patients can be sure that their cancer will not return.”
Professor Kristian Helin, chief executive of The Institute of Cancer Research, and a leading researcher of epigenetics and cancer, said the research adds to the growing body of evidence for the role of epigenetic regulation in cancer’s complex behaviour.
“We know that cancer will adapt and evolve to evade treatment, and this study shows how it will lie dormant to hide from treatment,” she said.
“Drugs targeting epigenetic modifications are already in development, and I hope that this research will pave the way to new treatments that prevent breast cancer from returning.”
Dr Tayyaba Jiwani, science engagement manager at Cancer Research UK, added: “Breast cancer survival has doubled in the UK over the last 50 years thanks to better detection and screening, but there are still more than 11,000 deaths from this type of cancer every year.
“Our research has made it increasingly clear that cancer cells can lie dormant in the body for many years before being triggered to reawaken, causing cancer to return. This study uses an innovative approach to analyse the genetics of these dormant cells and gain important insight into the mechanisms leading to dormancy.
“Although at an early stage, the findings reveal potential new targets for the development of innovative treatments that prevent breast cancer from coming back.”
Housing, work and fertility pressures are stopping many Britons growing the families they want, new research suggests.
A UK fertility report found that 79 per cent of people surveyed who had tried to conceive in the past five years would like more children than they currently have.
Among parents with one child, that figure rises to 88 per cent.
The report surveyed more than 1,000 people across the UK who had tried for a baby in the past five years.
While birth rates continue to fall, the findings suggest it is not because people no longer want children. Instead, many respondents said external pressures are making it harder to grow their families.
The findings, from wellness brand Wild Nutrition’s Fertility Disconnect report, highlight how financial pressures, fertility struggles and gaps in reproductive health knowledge are shaping modern family life in the UK.
Gail Madalena, fertility nutritional therapist at Wild Nutrition, said: “People often assume fertility begins the moment they decide to try [for a baby].
“In reality, egg and sperm health are shaped months and years earlier.
“By the time someone starts thinking about fertility, their body has already been responding to its environment for a long time.”
Among the biggest barriers, 26 per cent said career progression affected their family plans, 25 per cent cited housing affordability and lack of space, and 52 per cent said they required medical intervention during their fertility journey.
The report also found that almost a quarter of respondents had spent more than two years trying to conceive.
Trying for a baby can take a significant toll on mental health and relationships, especially for those navigating fertility treatment.
According to the research, 38 per cent of respondents said trying to conceive had negatively affected their mental health. That figure rose to 99 per cent among people undergoing fertility treatment.
Julianne Boutaleb is a perinatal psychologist.
She said: “Navigating a fertility journey is about so much more than medical appointments and procedures.
“It’s an emotional marathon that can take a huge toll on your mental wellbeing.
“Sadly, the stats show that 15 per cent of couples going through fertility treatment say their relationship has been irrevocably impaired.”
The report also highlighted the realities of secondary infertility, which affects around one in 20 people, challenging the assumption that having one child means conceiving again will be straightforward.
Researchers found many people felt under-informed about fertility, particularly younger adults.
Ten per cent of Gen Z respondents said they “know nothing” about fertility, while only one in five respondents said they know “a lot” about egg health.
The report also found that 60 per cent of women were unaware of fertility testing options, and one in five Gen Z respondents said they felt uncomfortable discussing fertility, even with their partner.
Around 40 per cent of those surveyed supported fertility education being included in schools, covering topics such as egg health, sperm health and hormonal health.
The report also explored how lifestyle and long-term health may influence fertility outcomes.
Many respondents said they only made changes once they started trying to conceive.
Some 44 per cent improved their diet when trying for a baby, while 32 per cent reduced alcohol intake at that stage.
The report also referenced emerging research that suggests ultra-processed foods and microplastics could have an impact on reproductive health.
While fertility conversations often focus on women, the findings showed male fertility issues are also affecting many families.
Seventeen per cent of respondents cited sperm health issues as a barrier to conception, while male factors contribute to around half of all fertility challenges.
Only one in four men said they would share fertility struggles with friends.
“Many causes of male infertility are entirely treatable yet so often the last resort is the first response,” said Ian Stones, co-founder at Test Him Ltd.
The findings come as UK birth rates remain below replacement level.
The report noted that the UK fertility rate is now 1.41, meaning that on average women give birth to 1.41 children over their lifetimes. The replacement rate, or rate that maintains population numbers, is 2.1.
It also said the average age of mothers has risen to 31, while birth rates are falling across most age groups except among over-40s.
“There is no single fertility story, and it is rarely a simple, linear narrative,” said Dr Zeynep Gurtin, lecturer in women’s health at UCL.
Dr Gurtin added that better fertility education, fairer access to treatment and more open conversations around infertility and pregnancy loss are needed.
Femtech World is thrilled to reveal the shortlist for the Fertility Innovation Award.
The award, sponsored by FinDBest IVF, celebrates a pioneering product, service or initiative that is transforming fertility care and support.
FinDBest IVF is a global B2B digital platform created to simplify and accelerate how IVF and ART manufacturers connect with trusted, pre-vetted distributors around the world.
This year’s nominees represent a remarkable breadth of approaches to fertility care: from clinic-floor breakthroughs to at-home hormone intelligence to truly borderless access.
Three companies made the cut, with each tackling a real, persistent barrier in reproductive health.
Congratulations to the shortlist and many thanks to everyone who entered.
Fertility Innovation Award Shortlist
HRC Fertility’s Needle-Free IVF is a pioneering advancement designed to transform one of the most challenging aspects of fertility treatment: daily hormone injections.
Developed by board-certified reproductive endocrinologist Dr Rachel Mandelbaum, this innovative approach reimagines how stimulation medications are delivered during IVF and egg freezing, dramatically improving the patient experience while maintaining the same trusted clinical outcomes.
Inspired by feedback from patients who struggled with the injection process, Dr Mandelbaum adapted an innovative drug-delivery system commonly used in other areas of medicine and applied it to reproductive care
Mira is a hormonal health technology company that provides lab-grade hormone testing and AI-driven insights to help women and couples understand their fertility.
The platform has already supported more than 200,000 couples on their fertility journeys worldwide, helping over 60,000+ users achieve pregnancy.
For some users, pregnancy rates have reached up to 89 per cent within six months, demonstrating how accurate hormone data can significantly improve fertility outcomes.
Founded in 2021 by Marija Skujina, a Certified Fertility Nurse Specialist accredited by the European Society of Human Reproduction and Embryology, with nearly 15 years of clinical experience at one of the world’s top IVF clinics, and having navigated her own fertility journey as a patient, Marija built the clinic she had always wished existed.
Plan Your Baby began with a bold, but simple mission – make best quality fertility and pregnancy available anywhere.
Plan Your Baby has created a new generation fertility and pregnancy clinic with patients accessing expert consultations remotely, while blood tests and ultrasound scans are available at over 450 locations across the UK, eliminating the exhausting travel burden that often forces people to take days off work, relocate appointments, or abandon treatment altogether
What happens now
The shortlist will be judged by a representative from category sponsor FindBestIVF, with the winner announced at a virtual event on June 19.
Winners will receive a trophy and be interviewed by a Femtech World journalist.
A common cholesterol drug could help weaken a fluid shield that helps ovarian cancer tumours survive, early lab findings suggest.
The findings do not show the drug treats ovarian cancer. But they suggest changing the environment the cancer depends on could make it more vulnerable to existing treatment.
A federally funded study at Duke University School of Medicine found that ascites, a build-up of fluid in the abdomen, may do more than cause discomfort.
Doctors can drain ascites to ease pain, improve mobility and make breathing easier, but the fluid may also help cancer cells survive and spread. It occurs in 90 per cent of people with advanced ovarian cancer.
According to the study, ascites acts as a shield, helping cancer cells evade ferroptosis, a form of cell death.
Ferroptosis is a kind of cellular rusting. It happens when iron inside a cell reacts with certain fats, causing the cell membrane to break apart.
Many metastatic cancer cells, meaning cells that float freely through the abdomen looking for new places to grow, are naturally vulnerable to this kind of damage.
“Doctors have mostly viewed ascites as a symptom rather than an active driver of disease,” said Jen-Tsan Chi, professor in the department of molecular genetics and microbiology and co-leader of the Cancer Biology Program at the Duke Cancer Institute.
“We’ve learned it gives cancer a survival advantage, which fills a major gap in understanding how ovarian cancer spreads.”
Scientists bathed cancer cell lines and patient-derived tumour cells in ascites collected from patients and watched how they responded to ferroptosis triggers.
The fluid protected cancer cells by changing how they store fats and control iron levels, effectively blocking cell death.
The protection required only trace amounts, with as little as 2 per cent immersion shielding cancer cells from destruction.
“What surprised us was how selective this effect was,” said Yasaman Setayeshpour, first author and graduate student in molecular genetics and microbiology at Duke School of Medicine.
“Ascites didn’t protect the cancer cells from other well-known types of cell death, like apoptosis or necrosis, it only blocked ferroptosis.
“To figure out why, we broke ascites down into major parts, like lipids, proteins, and small molecules, and tested what happened when each was removed.
“When we took the lipids out, the protective effect disappeared. That told us lipids are the key reason ascites helps these cancer cells survive.”
But researchers found an unexpected helper in bezafibrate, an older cholesterol drug used to lower triglycerides by altering how the body processes fats.
The cholesterol drug restored sensitivity to ferroptosis, but only when ascites was present. On its own, the drug did not trigger cell death or slow tumour growth in mice.
The drug’s impact depended on the cancer’s surroundings, in this case the fat-rich fluid bathing the tumour. Researchers found that targeting this environment, using repurposed drugs like bezafibrate, could leave cancer cells more exposed to existing cancer treatments.
Chi said the finding could have implications beyond ovarian cancer. Other cancers, including colorectal and pancreatic cancers, can also spread within the abdominal cavity.
“This work shows how much the environment around a tumour matters,” Chi said.
“Biological fluids like ascites don’t just give cancer cells a place to move. They actively help drive how cancer spreads.”
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