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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

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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.”

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Menopause start-up bags US$60m in funding

Midi Health aims to expand access to insurance-covered care for women in midlife and beyond

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Midi Health Series B round investors and founders, pictured from left: GV Executive venture partner Cathy Friedman, Midi Health co-founder Kathleen Jordan, Midi Health co-founder Jill Herzig, Felicis Ventures general partner Victoria Treyger, Operator Collective founder Mallun Yen, Midi Health co-founder Sharon Meers, Midi Health co-founder and CEO Joanna Strober, Emerson Collective managing partner Fern Mandelbaum, SemperViren partner Allison Baum Gates, GV general partner Frederique Dame

The US menopause start-up Midi Health has secured US$60m in funding, bringing the company’s total funding raised to date to US$100m.

The funding round was led by Emerson Collective, with support from additional investors, including GV (Google Ventures), Memorial Hermann, SemperVirens, Felicis, Icon Ventures, Black Angel Group, Gingerbread Capital, Able Partners, G9 and Operator Collective.

They joined a syndicate of primarily female-led investors including F7, Steel Sky Ventures, Avestria, Muse Capital, 1843 Capital, Anne WojcickiSusan Wojcicki, and K50 Ventures.

Founded with a mission to close this care gap, Midi is now the fastest-growing virtual clinic focused on treating women in perimenopause and menopause.

The California start-up, which expanded to all 50 states in November, aims to help women navigating midlife hormonal changes.

The company provides patients with care plans that include hormonal and non-hormonal medications, supplements and lifestyle coaching and has partnerships with major healthcare systems, such as Memorial Hermann and benefits platforms, such as Progyny and Cleo.

The additional investment round is hoped to help Midi expand insurance coverage, hire and upskill an additional 150 clinicians, diversify service lines, amplify the conversation around women’s health and scale to care for over one million women per year by 2029.

“We started Midi with just one specific focus: helping women access world-class, expert perimenopause and menopause care, covered by insurance, and we have been at the forefront of delivering on that promise,” Joanna Strober, CEO and co-founder of Midi, explained.

“But what we have also learned is that addressing the health concerns of women in midlife is more complex than simply treating hot flashes and prescribing hormone replacement therapy.

“Midi takes a multi-symptom, holistic approach to care designed to help women live their best, most productive and fulfilling lives—whether that involves medication, lifestyle coaching, natural supplements, or other support.

“Our goal now is to expand services and scope to continue this comprehensive, personalised care far beyond menopause.”

Women spend more than a third of their lives in perimenopause or menopause, with more than one billion women globally expected to be in these life stages by 2030.

Upwards of 85 per cent of women will experience menopausal symptoms that can negatively impact their productivity and quality of life, yet 75 per cent of women who seek care for these symptoms do not receive any treatment.

The primary reason is that only about one in five OB/GYNs, and even fewer primary care physicians, receive specialised menopause education or training.

“Historically, women’s healthcare has been neglected, with perimenopause and menopause having significant unmet needs,” said Fern Mandelbaum of Emerson Collective.

“Midi is providing expert, empathetic care coupled with comprehensive insurance coverage, finally addressing this gap and ensuring that all women receive the support they need and deserve.”

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Start-up launches London Underground campaign to break down period stigma

The two-week campaign seeks to challenge societal taboos surrounding menstrual health

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The Irish women’s health start-up Riley has launched an ad campaign on the London Underground to “take the fear out of periods”.

Riley, an eco-friendly period product subscription service, aims to take action against period poverty and democratise access to period products.

The company seeks to encourage the introduction of menstrual health policies and foster a workplace where discussions around periods are normalised.

Its two-week London Underground campaign, which coincides with the opening of its first office in London, is hoped to help destigmatise periods and normalise conversations around menstrual health.

“The idea behind this campaign comes from the fact that free period care in the office is often seen as an employee perk or a ‘nice to have’, when it should actually be an essential offering in every office,” Meaghan Droney, eCommerce manager at Riley, told Femtech World.

“Our aim with this campaign is to flip those current mindsets and get people to change their attitudes towards period care in the workplace.

“With 79 per cent of menstruators feeling unsupported in relation to their periods at work, this oversight is clearly fundamentally unfair and it’s time for change.

“We’re encouraging any and all businesses to get in touch with us so we can support them in introducing menstrual policies and free period care in their workplace to empower all employees, no matter their gender, to thrive and feel valued at work.”

Research by the Chartered Institute of Personnel and Development (CIPD) shows that only 12 per cent of UK companies provide support for menstruation and menstrual health, despite 85 per cent of women experiencing stress or anxiety when managing their period at work.

Data suggests that half of the women who take absence because of their menstrual cycle feel unable to tell their manager, underscoring the deep-rooted stigma around periods.

Fiona Parfrey, co-founder of Riley, said: “Access to safe and high-quality sustainable period care products not only demonstrates a commitment to employee welfare but also fosters a culture of empathy, equality, and respect, ultimately contributing to a more engaged and empowered workforce.

“Menstrual policies and free period care are a fundamental necessity for every individual in the workplace. It’s about ensuring that employees have the resources they need to maintain their wellbeing and productivity without interruption.”

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Singapore-based fertility centre sets up grant for couples struggling to conceive

This grant aims to support eligible Singaporean couples facing financial and family planning challenges

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A Singapore-based fertility centre is to set up a grant to support couples struggling to conceive.

Virtus Fertility Centre Singapore (VFCS) announced that it would set up a grant to support aspiring parents on their IVF journey.

The initial grant is set for at $50,000 SGD and, depending on the take-up rate over the next 12 fiscal months, VFCS plans to increase the pool to benefit more couples in the subsequent years.

The grant will cover the main costs associated with IVF treatments and procedures, including embryo retrieval and transfer, laboratory services and embryo prep. It will also be applicable to fresh and frozen egg transfers.

As grant recipients, their samples will similarly be given a radio frequency identification (RFID) tag, a service VFCS provides for all its patients. It locks the patient’s identity with the respective sample. The RFID identifies gametes—eggs, sperms, or embryos—at every stage of the IVF treatment.

According to VFCS, the grant will also include access to counselling services and wellness resources.

“I’ve witnessed firsthand the emotional toll and occasional frustration that infertility can take on individuals and couples, especially for some who are still young and healthy,” said Dr Roland Chieng, medical director at VFCS.

“The common deterrent of going for fertility treatment is always associated with the cost, more so in a private care setting where their only source of funds is through Medisave.

“By alleviating their financial concerns, we hope ReadyBaby Fertility Grant empowers patients to approach their IVF journey, focusing on their clinical needs and working towards a healthy pregnancy and less on financials.

“With access to the necessary treatments and support, patients can embark on their path to parenthood with renewed confidence, knowing they have the clinical resources and guidance they need to navigate this journey,” he added.

Tim Kwan, VFCS’s managing director, said: “We believe every couple deserves the opportunity to experience the profound joy of parenthood.

“With the ReadyBaby Fertility Grant, we aim to support aspiring couples on their IVF journey and help them bring new life into the world.”

To be eligible for the grant, applicants must be married Singaporean couples diagnosed with medical infertility by a fertility specialist and first-time parents who have not tried IVF before.

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