Pregnancy
Research roundup: Overcoming EGFR-targeted therapy resistance in breast cancer, and more
Femtech World explores the latest developments in women’s health research – from overcoming EGFR-targeted therapy resistance in breast cancer to understanding obesity’s role in triple-negative breast cancer, and more.
EGFR-targeted therapy resistance in breast cancer
Researchers have reviewed current research on why Epidermal Growth Factor Receptor (EGFR)-targeted therapies often fail in breast and head and neck cancers.
The article explores how cancer cells evade these treatments by activating alternative survival pathways and offers an in-depth look at the molecular barriers to EGFR inhibition, providing insights that could inform the development of more effective and durable treatments.
EGFR is a critical protein that regulates cell growth and survival, and it is frequently overexpressed in breast and head and neck cancers. Although therapies targeting EGFR showed early promise, resistance has become a significant challenge.
In breast cancer, resistance mechanisms include the movement of EGFR from the cell surface into the nucleus, where it promotes DNA repair, as well as ligand-dependent activation that helps tumour growth despite therapy.
The review describes how tumour cells in these cancers commonly activate other receptor tyrosine kinases (RTKs), such as MET, AXL, and RON, to continue growing even when EGFR is blocked.
By analysing these resistance mechanisms, the authors highlight combination therapies from current research that target EGFR and other key molecular pathways.
Strategies such as dual inhibition of EGFR and MET or blocking inflammation-driven survival signals may enhance treatment outcomes.
Several clinical trials are evaluating these approaches in patients.
For example, in breast cancer, combinations of EGFR inhibitors with chemotherapy and immune checkpoint inhibitors are being tested to improve responses, particularly in triple-negative breast cancer.
These efforts aim to overcome resistance and provide more effective treatment options for patients with EGFR-driven tumours.
The review also emphasises the necessity of identifying biomarkers to predict which patients are most likely to benefit from EGFR-based therapies.
Screening women with diabetes for intent to conceive at every doctor visit
Adverse pregnancy outcomes such as miscarriages or birth defects are common in individuals with pre-existing diabetes and are often related to modifiable factors such as maternal high blood sugar and body mass index (BMI).
With this in mind, a new, joint guideline released by the Endocrine Society and the European Society of Endocrinology (ESE) has recommended that women with diabetes receive proper preconception care.
This includes access to emerging diabetes technology and therapeutics to manage their blood sugar before, during and after pregnancy.
Screening women of reproductive age who have diabetes for intent to conceive at every reproductive, diabetes and primary care visit helps ensure they get the appropriate preconception care and reduces health risks.
Care suggestions from the guidelines include screening by asking all women with diabetes of reproductive age about intent to conceive at every reproductive, diabetes and primary care visit; timing delivery before 39 weeks for pregnant individuals with diabetes as the risks associated with continued pregnancy may outweigh those of early delivery; discontinuing anti-obesity medications called GLP-1s prior to pregnancy; and, avoiding prescribing metformin in pregnant individuals with preexisting diabetes already on insulin.
Further suggestions include using diabetes technology, recommending hybrid closed loop systems for pregnant individuals with type 1 diabetes; and suggesting that women with diabetes use contraception until they are ready to become pregnant.
Premenstrual symptoms linked to increased risk of cardiovascular disease
A new study has revealed that women diagnosed with premenstrual symptoms have a slightly increased risk of developing cardiovascular disease later in life.
Premenstrual symptoms include premenstrual syndrome (PMS) and the more severe form, premenstrual dysphoric disorder (PMDD).
The study followed more than 99,000 women with premenstrual symptoms for up to 22 years, comparing their health with women without these symptoms – both in the general population and by comparing them with their own sisters to take into account hereditary factors and upbringing.
The results show that women with premenstrual symptoms had about a 10 per cent higher risk of developing cardiovascular disease.
When the researchers also looked at different types of cardiovascular disease, they found that the link was particularly strong for heart rhythm disorders (arrhythmias), where the risk was 31 per cent higher, and for stroke caused by a blood clot, where the risk was 27 per cent higher.
Even after the researchers took into account other factors such as smoking, BMI and mental health, the link between premenstrual symptoms and increased disease risk remained.
Research has not yet identified the cause of this link, but the researchers behind the study suggest three possible explanations.
One is that women with premenstrual symptoms may have a disrupted regulation of the renin-angiotensin-aldosterone system (RAAS), which controls blood pressure and fluid balance in the body, among other things.
The second is that these women have increased levels of inflammation in the body, which is a known risk factor for atherosclerosis and other heart problems.
Finally, it may be because women with premenstrual symptoms may have metabolic abnormalities, which are linked to an increased risk of both stroke and heart attack.
Obesity’s role in triple-negative breast cancer
Among the various subtypes of breast cancer, triple-negative breast cancer (TNBC) stands out due to its aggressive nature and poor prognosis.
It is characterised by the absence of three critical hormone receptors: oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, which are common targets for breast cancer therapies.
Consequently, TNBC lacks targeted treatment options, relying primarily on conventional cytotoxic therapies, often referred to as chemotherapy in which drugs kill or damage cancer cells.
This limitation contributes to the subtype’s high recurrence rates and significantly lower survival rates compared to other forms of breast cancer.
Researchers have now discovered that exosomes, messenger nanovesicles that carry proteins, RNA, and other molecules to other cells, that are released into the blood by different organs and tissues in obese, insulin-resistant models, carry signals that turn otherwise slow-moving TNBC cells into highly mobile, invasive cells.
This is the first time a study has shown that exosomes from an obese, diabetic environment directly cause this aggressive change in TNBC, and that Rho-proteins (molecular switches that turn “on” or turn “off” signal transduction pathways) play a key role in driving the change.
According to the researchers, by revealing how obesity-driven exosomes push aggressive breast cancer to spread, they hope to unlock new blood tests and drug targets, like Rho-protein inhibitors that stop this deadly process.
“These findings support the development of clinical tests to quantify obesity-derived exosomes in patient plasma as noninvasive biomarkers of metastatic risk, allowing earlier identification and tailored management of aggressive TNBC,” said corresponding author Gerald Denis, Shipley Prostate Cancer Research professor and professor of pharmacology, physiology and biophysics.
“Ultimately, our goal is to improve survival and quality of life for patients facing both metabolic disease and hard-to-treat cancers.”
Light exercise and less sitting may reduce pregnant women’s risk of serious blood pressure complications, according to a new study.
Researchers have proposed a daily activity and sleep guide that they say was linked to a nearly 30 per cent lower risk of hypertensive disorders of pregnancy.
The suggested pattern includes fewer than eight hours of sedentary time, at least seven hours of light physical activity, around 22 minutes of more intense activity and nearly nine hours of sleep.
The University of Iowa-led study examined the daily behaviours of 470 pregnant women across all stages of pregnancy.
Participants wore monitors that measured physical activity over 24-hour periods and recorded how long they spent asleep.
Hypertensive disorders of pregnancy include chronic high blood pressure, gestational hypertension and pre-eclampsia.
Gestational hypertension is high blood pressure that develops during pregnancy, while pre-eclampsia is a potentially serious condition involving high blood pressure and signs that organs may be affected.
Sedentary behaviour means being mostly inactive, such as sitting or lying down.
Light physical activity can include casual walking, moving around the home or standing.
Moderate to vigorous activity includes movement such as brisk walking, where breathing and heart rate increase.
Kara Whitaker, associate professor in the department of health, sport, and human physiology at Iowa and corresponding author of the study, said: “We are identifying the optimal composition of movement behaviours across the day associated with the lowest risk of developing HDP and the most improved health outcomes.
“This blueprint holds for each and every trimester of pregnancy.”
Study participants were enrolled at sites in Iowa City, Pittsburgh and Morgantown, West Virginia.
The women wore activity and sleep monitors for at least one week during each trimester of pregnancy.
Four in five participants were non-Hispanic white and nearly a quarter lived in rural areas.
The data showed a steep rise in risk among pregnant women who were sedentary for more than 10 hours a day.
Women who increased light physical activity to at least four hours a day reduced their risk of hypertensive disorders of pregnancy to 15 per cent from 30 per cent.
Whitaker said: “Just moving around more seems to have significant health benefits.
“And I think it also may be a more feasible target for women who are pregnant who are not exercising regularly.”
The researchers said they were surprised that longer durations of moderate to vigorous physical activity did not appear to provide additional benefit.
Sleep beyond a certain duration also did not appear to bring major further benefits.
Whitaker said: “Through this study, we are providing evidence that reducing sedentary behaviour and engaging in light physical activity are important, and maybe more important, when it comes to pregnancy and health.”
The findings may be relevant beyond pregnancy because clinical research has shown that women who develop hypertensive disorders of pregnancy are more than twice as likely to develop heart disease later in life.
Cardiovascular disease includes conditions affecting the heart and blood vessels, such as heart disease and stroke.
Whitaker said: “We know that cardiovascular disease is the number one killer of women, and if we can intervene in pregnancy and prevent women from developing a hypertensive disorder of pregnancy, we are putting them on a better trajectory, away from cardiovascular disease and toward more optimal cardiovascular health.”
The study was published online on June 10.
A second study, published online on May 27, looked more closely at the ratio and type of sedentary behaviour and light physical activity linked to a lower risk of hypertensive disorders of pregnancy.
Whitaker is a lead co-author on that study.
Co-authors in the June 10 study include Alex Crisp, Jaemyung Kim, Karina Smith, Donna Santillan, Mark Santillan and Bridget Zimmerman, from Iowa; Jacob Gallagher, from Iowa State University; Melissa Jones, from Oakland University in Michigan; Bethany Barone Gibbs, Katrina Wilhite, Alexis Thrower and Iqra Sheikh, from West Virginia University; and Sabera Rahman, Janet Catov, Christopher Kline and Maisa Feghali, from the University of Pittsburgh.
The National Institutes of Health, the University of Iowa Institute for Clinical and Translational Science, the University of Pittsburgh Clinical and Translational Science Institute and the West Virginia Clinical and Translational Science Institute funded the research.
A £50m maternity consortium will bring together UK clinicians, researchers and communities to tackle the most critical gaps in maternal care.
Funding from the National Institute for Health and Care Research has established the NIHR Inequalities Challenge: Maternity Disparities Consortium under the leadership of the University of Birmingham and Newcastle University.
Higher education bodies, NHS organisations, community groups and voluntary organisations from across the UK will work together through the programme.
The NIHR has committed £50m over five years to support research led by clinicians, researchers and communities across the consortium.
Professor Joht Singh Chandan, consortium co-lead for research at the University of Birmingham, said: “National attention on maternity safety and equity has never been greater, but ambition must now be matched by evidence and implementation.
“Through this consortium, we will work across the UK to understand what works, for whom and in what contexts, and to ensure that research leads to practical changes in care for the women, babies and families who need them most.”
The launch comes at a pivotal moment for UK maternity care, with growing national attention on improving safety, equity and women’s experiences of care.
The government’s renewed Women’s Health Strategy highlights the need to improve care before and between pregnancies for underserved communities.
Against that backdrop, the consortium will generate the evidence, interventions and research capacity needed to help turn national ambition into practical improvements for women, babies and families.
University of Birmingham is leading work to improve maternity care pathways across the antenatal, intrapartum and postnatal periods.
Antenatal care covers pregnancy before labour, while intrapartum care refers to care during labour and birth.
The consortium will examine how women and families can be better supported before pregnancy and between pregnancies.
This includes improving access to advice and care that can help people prepare for pregnancy, manage existing health conditions and reduce risks before they build up.
Other research will focus on improving care during pregnancy, birth and the early weeks after birth.
This will include work on major causes of poor maternal health, such as high blood pressure, diabetes in pregnancy, obesity, perinatal mental health and complications during recovery after birth.
Professor Judith Rankin OBE, consortium co-lead for research and capacity development at Newcastle University, said: “This funding represents a critical opportunity to make the step change we need to improve outcomes for women and their babies.
“Alongside the research, the Consortium will be investing in tomorrow’s research leaders today to ensure we have the capacity to deliver on improving pregnancy outcomes, access to, and experience of, care.”
The University of Liverpool has secured £1.8m to test a device for postpartum bleeding and launch a new women’s health studio.
The PPH Butterfly is designed to help control postpartum haemorrhage, which is severe bleeding after childbirth and a leading cause of maternal death worldwide.
The funding will support research into how the device can be used in clinical practice and generate evidence to inform its wider adoption.
The university has launched the Women’s Health Innovation Studio, known as the WIN Studio, alongside the project.
The £1.8m initiative is predominantly funded by the National Institute for Health and Care Research, which is providing £1.5m, with additional support from the university.
The PPH Butterfly project will involve a multi-centre clinical trial across the UK and a global feasibility study looking at how practical it would be to use the device in different healthcare settings.
The WIN Studio is led by Andrew Weeks, professor of international maternal health care at the University of Liverpool and a senior investigator at the National Institute for Health and Care Research, and Dr Teesta Dey, a tenure track fellow in the department of women’s and children’s health.
Dr Dey will also lead the PPH Butterfly project.
Its work will cover conditions linked to female biology, including endometriosis, menopause and pregnancy-related complications.
It will also support technologies for diseases that affect women differently or disproportionately, even when they are not usually classed as gender-specific conditions.
Dr Dey said: “Women’s health has often been marginalised within healthcare systems and innovation markets, resulting in treatments, devices and care models that fail to adequately account for women’s specific needs. WIN Studio seeks to change this status quo and reconfigure how health technologies are conceived and delivered.
“The funding from NIHR for this £1.8m project is precisely the kind of innovation the WIN Studio exists to foster: clinically urgent, women-centred, and with the potential to save lives at scale.”
The studio recently hosted an event at Liverpool Women’s University Hospital as part of the Liverpool City Region Combined Authority’s Innovation Investment Fortnight.
Seven innovations are currently undergoing clinical testing through the studio, with three developed internally.
The studio will work closely with NHS University Hospitals Liverpool Group and provide clinical, regulatory and commercial support to people developing women’s health technologies.
It will also involve patients and members of the public in shaping research priorities and product development.
Its wider programme includes collaborations involving clinicians, engineers, economists, academics and policymakers.
The project team says the PPH Butterfly is a simple, low-cost device designed to control severe bleeding quickly and with minimal training.
According to the team, postpartum haemorrhage causes around 70,000 deaths globally each year, equal to about one death every seven minutes.
The device previously received £1.1m in funding from the National Institute for Health and Care Research.
The latest £1.5m grant will support a randomised UK trial, in which participants are allocated to different treatment groups by chance, and a global feasibility assessment.
Weeks said: “In an area where women face deep health inequalities, WIN Studio has a vital role to play. By working in partnership with the NHS, local government and communities, we can ensure that research leads to real-world impact.
“Liverpool has a highly integrated ecosystem of academic, clinical and commercial expertise. By bringing these together under a single platform, the WIN Studio aims to act as a national exemplar for equitable health innovation. Transforming the way medical technologies are developed is essential to addressing gender disparities in healthcare outcomes.”
Another product supported by the university, the LifeStart Trolley, has already reached commercialisation.
The small mobile resuscitation trolley allows newborn care to be carried out at the bedside while the baby’s umbilical cord remains intact, enabling delayed cord clamping.
Delayed cord clamping means waiting before cutting the cord so blood can continue flowing from the placenta to the baby after birth.
Clinical trials conducted around 10 years ago found that life-saving care could be provided successfully at the bedside using the trolley.
It was later commercialised by Inspiration Healthcare and is now used in more than 70 UK maternity units and in 36 countries, including Norway, Italy and the US.
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