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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.”
Our sister publication Health Tech World brings its first live event to London this summer, gathering the people building, buying and regulating healthcare AI for a single afternoon. With a full line-up confirmed and two months to go, tickets are open now, and this first edition is one to book early.
Health Tech World Live, the debut live event from FemTech World’s sister title Health Tech World, makes its first appearance on Friday 21 August, bringing clinicians, founders, developers, NHS commissioners and investors together at Teesside University London in Stratford for an afternoon on where healthcare AI goes next. The programme is confirmed, and with two months to go, it is worth booking your place while the diary is still clear.
The line-up for this first edition reads like a who’s-who of UK health AI. Speakers include Dr James Harmsworth King, Chief Medical Strategy Officer at Numan, fresh from the MHRA’s AI Airlock; Dr Sonia Szamocki, founder and CEO of 01Health; Hugo Dragonetti of NHS London Procurement Partnership; Mikael Kågebäck, CTO at Sleep Cycle; Max Gattlin, Commercial Director at X-on Health; and Marcus Vass, Head of Digital Health at Osborne Clarke, with proceedings chaired by Alastair MacColl.
Across six sessions, the afternoon moves from scaling specialist care and smarter NHS procurement, through responsible delivery and consumer AI, to fair access to GP care and the regulation underpinning all of it. Between the talks, delegates get time with the speakers and the Health Tech World editorial team, the kind of access that is hard to come by anywhere else.
It is shaping up to be one of the summer’s standout dates in health tech, and a launch worth being part of from the start. If you are planning to be there, now is the time to get it booked.
The future of healthcare AI: strategies, opportunities and vital insights
When: Friday 21 August 2026, 12 noon to 4pm
Where: Teesside University London Campus, Queen Elizabeth Olympic Park, 14 East Bay Lane, London, E15 2GW
Tickets: £99
Immunotherapy may temporarily restore fertility in women with autoimmune premature ovarian insufficiency, a pilot study suggests.
Three of the 10 women who received treatment later gave birth to healthy babies.
Premature ovarian insufficiency, or POI, affects just over three per cent of women worldwide and occurs when the ovaries stop functioning before the age of 40.
The condition significantly reduces fertility and can have several causes, including autoimmune processes and genetics.
Researchers at Karolinska Institutet examined whether immunotherapy could make the ovaries temporarily responsive to hormonal stimulation in women with POI caused by autoimmunity.
The study included 12 women aged between 18 and 35 with autoimmune POI.
Two withdrew before treatment began. The remaining 10 underwent ovarian hormone stimulation before receiving rituximab and again four to six months after treatment.
Rituximab is an approved and well-established medicine used to treat several autoimmune conditions and cancers.
None of the women responded to ovarian stimulation before receiving the drug.
After treatment, six developed follicles that made it possible to retrieve eggs in response to ovarian stimulation.
Follicles are small sacs within the ovaries where eggs develop.
Professor Angelica Lindén Hirschberg, the study’s first author and a professor at Karolinska Institutet’s Department of Women’s and Children’s Health, said: “The results show that in some women there remains an egg reserve that can be activated when the autoimmune process is suppressed.”
In five women, mature eggs could be frozen or fertilised.
Three later had embryos transferred and all three gave birth to healthy babies.
For safety reasons, the embryo transfers took place no earlier than one year after treatment.
One serious side effect was reported and was linked to the hormone stimulation rather than the immunotherapy.
Women with autoimmune POI commonly have other autoimmune diseases.
All six women who responded to the treatment also had autoimmune Addison’s disease, a condition in which the immune system destroys the adrenal glands.
The study was a proof-of-concept investigation without a control group and involved a small number of participants, meaning the findings must be interpreted cautiously.
A proof-of-concept study is an early investigation designed to assess whether an approach could work before it is tested more widely.
Professor Lindén Hirschberg said: “This is a first step. To determine whether the method is effective and safe, larger, randomised studies are required.”
The research team has launched a larger randomised study.
The work was carried out by researchers at Karolinska Institutet, Karolinska University Hospital and the University of Bergen.
It was funded by organisations including the Swedish Research Council, the Knut and Alice Wallenberg Foundation, the Novo Nordisk Foundation and Region Stockholm.
The researchers reported no conflicts of interest.
POI is also linked to long-term health risks caused by oestrogen deficiency, including osteoporosis, an increased risk of cardiovascular disease, cognitive decline and poorer mental and sexual wellbeing.
Hormone replacement therapy can relieve menopausal symptoms and reduce many of these risks, but no treatment has been reliably shown to restore fertility in women with POI.
Egg donation was previously the only option for women with the condition who wanted to become pregnant.
Xella Health has launched what it calls the first AI precision health platform built for the XX chromosome.
The company says it aims to address a lack of diagnostic precision and clinical research focused on female biology.
Women make up half of the population and account for 80 per cent of consumer healthcare decisions, but research into women’s health has historically received less funding than male-focused studies.
Kelly Lacob, Xella Health co-founder and chief executive, said: “Women have been trapped in a diagnostic dark age experiencing debilitating symptoms like severe period pain, bloating and GI issues, exhaustion, and brain fog, routinely dismissed by the healthcare system.
“This dismissal results in women being diagnosed four years later than men, on average, for the same conditions, and a seven-to-10-year delay for women to receive an accurate diagnosis for conditions like endometriosis.
Stalling necessary care and treatment results in prolonged suffering with chronic pain, heightened infertility risks, and declining mental health.
Xella is here to replace the systemic medical gaslighting women have endured for generations.
We are handing women the evidence and information they need to advocate for themselves and secure faster, accurate diagnoses before early-stage conditions spiral.”
Xella says its AI examines billions of data points from clinical information and multi-omic biomarkers to assess the probability of more than 130 conditions specific to female biology.
Multi-omic data combines information from several biological areas, including genes, proteins and hormones.
The conditions assessed include polyendocrine metabolic ovarian syndrome, or PMOS, formerly known as polycystic ovary syndrome, as well as perimenopause and endometriosis.
Xella was founded by Lacob, Adriana Dantas and Dr Jesus Ching, who developed the concept while working together on molecular diagnostics at Mammoth Biosciences.
The founders say the platform is designed to provide information about possible underlying causes through advanced testing and long-term care of a kind often available only through expensive concierge services.
They drew on personal experiences to build a service intended to identify small changes in a woman’s biological baseline.
Members complete an initial health questionnaire before having blood taken at a local partner laboratory such as Quest or Labcorp.
A phlebotomist can also visit a member’s home for an additional charge.
The company’s AI analyses biomarker data from genomics, proteins and hormones alongside symptoms, lifestyle risks and medical history.
Xella says this information is used to screen for more than 130 female-specific conditions, including PMOS, Hashimoto’s disease, premenstrual dysphoric disorder, endometriosis and perimenopause timelines.
Hashimoto’s disease is an autoimmune condition in which the immune system attacks the thyroid gland.
Premenstrual dysphoric disorder, or PMDD, is a severe form of premenstrual syndrome that can cause significant emotional and physical symptoms.
The results are processed through Xella’s own dry laboratory, which the company says is certified under the US Clinical Laboratory Improvement Amendments and accredited by the College of American Pathologists.
A dry laboratory analyses data using computing and other non-experimental methods rather than carrying out traditional laboratory procedures.
The findings are turned into a personalised healthcare plan and reviewed with a certified telehealth doctor.
The doctor may recommend immediate clinical action, including personalised hormone therapy or referrals to genetic counsellors, pelvic floor physiotherapists and reproductive endocrinologists.
Reproductive endocrinologists are doctors who specialise in hormones, fertility and reproductive health conditions.
Dantas, co-founder and chief operating officer, said: “Women’s health data has historically been treated in isolated silos – a hormone test here, an ultrasound there – but no one was connecting the dots across the entire biology.
“By tracking unique biological patterns longitudinally across cycles and life stages, we aren’t just providing data, but a clear path forward.”
Xella’s clinical advisers include Dr Allison Kurian, director of Stanford Women’s Clinical Cancer Genetics Program and professor of medicine, epidemiology and population health at Stanford.
They also include Dr Lynn Westphal, a reproductive endocrinology and infertility specialist and chief medical officer of Kindbody.
Xella has received US$4.7m in angel and pre-seed funding from Precursor Ventures, Capital F, Ulu Ventures and Swizzle Ventures.
Other funds and angel investors from healthcare, diagnostics and consumer technology also participated.
Margaret Coblentz, co-founder and general partner of Capital F, said: “Women’s health is one of the highest-momentum categories in the market today, driven by a US$15tn female economy.
“Xella represents exactly how Capital F sees women’s health evolving: deep clinical expertise paired with a consumer-first mindset, and a genuine opportunity to unlock the next generation of healthcare.”
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