A new cancer drug may be able to inhibit both tumor growth and the spread of aggressive prostate cancer. This is shown in a study conducted by researchers at Umeå University together with international collaborators, published in the journal Signal Transduction and Targeted Therapy.

“The new drug has been developed to prevent metastasis, and we are very pleased and proud that we have been able to identify the mechanisms that drive cancer cell growth, invasiveness and metastatic spread,” says Maréne Landström, professor of pathology at the Department of Medical Biosciences, Umeå University, who led the study.

Prostate cancer is one of the most common cancers among men. In most cases, the tumor grows slowly and is not life-threatening. However, in some patients, the disease develops into an aggressive form that spreads to other parts of the body, primarily the lymph nodes and bones.

The researchers have developed a fully human antibody. This means it is composed entirely of human proteins, making it suitable for use as a therapeutic drug. In preclinical studies, the antibody successfully halted both tumor growth and metastasis in an aggressive form of prostate cancer. The new treatment works through a novel mechanism of action, leading researchers to believe that the risk of side effects also may be reduced.

The results demonstrate that the treatment performs as intended, marking an important milestone in the development of a new drug for future patients.

“This is a promising step forward, but several important stages remain before the treatment can benefit patients. We still need to conduct additional safety studies, and the treatment must be approved by regulatory authorities in Europe or the United States,” says Landström.

The driving force behind this research is the ambition to improve the prognosis and quality of life for men with advanced prostate cancer. The current study has been ongoing for several years and, according to Landström, its success is the result of contributions from many individuals and organizations.

An important part of the project has been the collaboration with drug development experts at the SciLifeLab Drug Discovery and Development Platform, who contributed to the development of the antibody on which the study is based.

“The next step is to investigate whether this treatment can also be used against other types of solid tumors. We hope that our work will ultimately contribute to the development of a new cancer drug that can benefit patients,” says Landström.

Modern IVF treatment can now achieve substantially higher success rates than historical approaches while dramatically reducing twin and triplet pregnancies, according to new research presented at the 42nd Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE). The study abstract was published in Human Reproduction.

In one of the largest IVF studies of its kind, researchers analyzed outcomes from 18,396 women undergoing their first IVF cycle between January 2012 and December 2021 across seven Australian fertility clinics, with follow-up through December 2023.

The research found that modern IVF clinical practices achieved a 68.2% cumulative live birth rate over three treatment cycles, while using single embryo transfer in 95.3% of embryo transfers and maintaining a multiple birth rate of just 2.9%.

The findings mark a notable improvement on historical IVF outcomes. Earlier studies, conducted before the widespread adoption of modern IVF laboratory techniques, reported three-cycle cumulative live birth rates of around 53%–59%, often alongside multiple pregnancy rates exceeding 20%.

How the outcomes were measured

The researchers say the improved outcomes likely reflect advances including blastocyst culture, embryo vitrification, freeze-all strategies and optimized frozen embryo transfer protocols, now widely used in contemporary IVF care.

Researchers examined cumulative live birth rates across up to three IVF cycles using contemporary clinical protocols, including extended blastocyst culture (day 5–6 embryo development), embryo vitrification (rapid freezing) and elective freeze-all approaches where appropriate. Women using donor eggs, frozen eggs or specific genetic testing pathways were excluded from the analysis.

Across all women, the cumulative live birth rate over three treatment cycles reached 58.7% using intention-to-treat analysis and 68.2% using optimal per-protocol analysis.

Success rates varied substantially by age. Women under 35 achieved an optimal cumulative live birth rate of 84.5%, compared with 74.4% for women ages 35–37, 57.7% for women ages 38–40 and 30.1% for women ages 41–42.

How blastocyst culture changed IVF

Lead author Dr. Dean Morbeck said the findings reflect a decade of incremental advances in IVF laboratory and clinical practice.

“The biggest shift has been that blastocyst culture has moved from being an exception to becoming the default,” Morbeck explained. “That change drove improvements across IVF laboratories, including reduced oxygen conditions, purpose-built incubators and minimized disruption to embryos during culture.”

“Blastocyst culture also became much more effective with vitrification, which dramatically improved embryo survival after freezing and warming, making frozen embryo transfer outcomes comparable to fresh transfers. Together, these advances enabled approaches such as freeze-all treatment, where embryos are transferred one at a time later, rather than during the initial stimulation cycle.”

The twin trade-off fades

The study also examined changes over time, comparing outcomes before and after laboratory improvements introduced from 2016 onward, including single-step culture medium and time-lapse embryo culture.

Between 2012–2015 and 2017–2021, the proportion of fertilized eggs developing into usable blastocysts increased from 48.3% to 57.6%, while single embryo transfer increased from 92.8% to 97.3%. Over the same period, the multiple birth rate fell from 3.2% to 2.7%.

Morbeck said the findings challenge the longstanding assumption that transferring multiple embryos is necessary to maximize IVF success.

“For many years, transferring two embryos increased the chance of pregnancy from any one transfer, but often came with twin pregnancy rates approaching 30%,” he explained. “What our data show is that this trade-off has largely disappeared.”

“Across more than 18,000 women, we achieved strong cumulative live birth rates while using single embryo transfer in 95% of cases and maintaining a twin birth rate under 3%. A concerted effort to reduce twin pregnancies has not cost patients their chance of taking home a baby—it has coincided with that chance increasing.”

Strong results without routine PGT-A

The findings also suggest that strong IVF outcomes can be achieved without routine use of preimplantation genetic testing for aneuploidy (PGT-A)—a test used to screen embryos for chromosomal abnormalities before transfer—in all patients.

PGT-A was used in one or more treatment cycles in 25% of women included in the study. However, Morbeck noted that most live births occurred without routine embryo genetic testing.

“PGT-A has an important role for some patients, particularly women of advanced maternal age and those with recurrent pregnancy loss,” he said. “But our findings should reassure many patients that strong IVF outcomes are achievable without routine genetic testing necessarily being required.”

Steady gains, safer treatment

Discussing the implications of the findings, Morbeck said the results support continued efforts to increase access to single embryo transfer internationally. “The future of IVF is continuing to improve the success rate of each embryo transfer while maintaining the safety gains we’ve achieved,” he said.

Reflecting on the significance of the research, Professor Borut Kovacic, chair-elect of ESHRE, said, “Improvements in IVF are typically driven by steady, incremental advances rather than dramatic breakthroughs.

“This study demonstrates that optimizing laboratory practices, adhering to evidence-based guidelines and adopting a relatively conservative treatment approach can progressively increase cumulative live birth rates while reducing multiple births—two outcomes that matter most to patients seeking a safe and cost-effective route to parenthood within a single stimulation cycle.”

A new HIV vaccine developed by La Jolla Institute for Immunology (LJI), Scripps Research scientists and IAVI has the potential to protect humans from developing HIV infection and AIDS. This HIV vaccine is the first to generate a high number of “broadly neutralizing” virus-fighting antibodies in primates. The research is published in the journal Nature.

“This feels like a huge success,” says LJI Professor and Chief Scientific Officer Shane Crotty, Ph.D., who co-led the research with Scripps Research Professor William Schief, Ph.D. “We constructed a successful vaccine from the ground up, which required a deep understanding of the immune system.”

This work is the result of 14 years of collaboration between La Jolla Institute for Immunology and Scripps Research, as part of the Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD).

“This has been one of those Apollo moon mission-type projects, where there is an exceptional goal and the team has to accomplish myriad discoveries and inventions along the way,” says Crotty.

Outsmarting HIV

The new vaccine works by intervening in a process called B cell maturation. B cells make antibodies. Like many immune cells, B cells have an early “naive” stage before they are ready to make antibodies. B cells start to mature once they get the signal that a pathogen, such as a virus, is trying to attack. B cells see pieces of that pathogen’s molecular structure and start producing antibodies that can bind to that structure and halt infection.

It can take a little while for B cells to find the right “bull’s-eye” on a pathogen. But B cells keep trying. As they mature, B cells tweak their antibody production, refining antibody structures to bind to a pathogen in just the right vulnerable spots.

Scientists describe B cell development as a training process or boot camp. In most cases, the body is left with a well-honed B cell army.

HIV is hard to beat because it doesn’t give B cells a chance to develop effective antibodies. The first problem is that HIV disguises itself from the immune system. The virus is wrapped in an ever-shifting cloak of sugar molecules, called glycans. This lets HIV sneak undetected past human cells, which are also covered in glycans.

The second big problem is that HIV mutates very quickly.

“The worldwide diversity of HIV mutations is extraordinary. Even the diversity within one individual person living with HIV is dramatic,” says LJI Instructor Patrick Madden, Ph.D., who served as study co-first author with Jon Steichen, Ph.D., an institute investigator at Scripps Research.

The third problem is that HIV changes its shape when it infects human cells. Even if B cells get a glimpse of its viral structure—snap!—the structure changes.

Taken together, these problems rarely give B cells a chance to hone their antibody responses against HIV. Even if a B cell manages to make neutralizing antibodies, the virus can mutate or change its shape, rendering those antibodies useless.

The LJI and Scripps Research teams spent years hunting for “broadly neutralizing” antibodies that can actually bind to HIV and recognize key viral structures, even if the rest of the virus mutates. These antibodies are very rare, but they can be found in blood samples from a small number of people living with HIV.

An effective HIV vaccine would need to prompt the immune system to make these same broadly neutralizing antibodies.

“How could we flip the whole immune response on its head so the rare responses become the common responses? That was a critical challenge we faced,” says Crotty.

Testing the new vaccine

It was time to go back to B cell boot camp. The scientists studied what made the HIV-fighting B cells special. Then they reversed the process to see exactly how those B cells matured. By looking back at the maturation process, the researchers could track how the B cells changed when they saw specific pieces of the HIV structure.

The team discovered that B cells matured to make broadly neutralizing antibodies after they got an early look at parts of HIV’s outer “envelope” protein. Because these viral sites sparked an immune response, scientists would call them “antigens.”

An effective HIV vaccine would likely need to include models of these antigens. The antigens would work like mug shots of America’s most wanted. If B cells saw those antigens early and often, they would get really good at recognizing and even neutralizing HIV.

“We were trying to mimic the progression of those neutralizing antibodies,” says Madden.

In a feat of molecular engineering, the Schief Lab developed vaccine molecules that resembled the real HIV antigens. The scientists then worked with Emory National Primate Research Center to test this potential HIV vaccine in a nonhuman primate species called rhesus macaques.

The researchers first administered a “priming” vaccine meant to activate each animal’s naive B cells. The animals then received a series of “shepherding” booster shots to help their B cells develop along the right path.

“This series of vaccinations will guide, or ‘walk,’ a B cell from its naive state to its broadly neutralizing state,” says Madden.

This new type of vaccine approach is called “germline targeting” because it targets naive B cells in their “germline” or naive form, before they begin their training process.

The scientists found that around 44% of the animals went on to produce broadly neutralizing antibodies against HIV in their blood. These antibodies were impressively abundant.

“We succeeded in taking ultra-rare antibody responses and turning them into common responses by the end of the vaccination process,” adds Crotty.

In related research recently published in Nature Immunology, the researchers reported a new strategy to accelerate related vaccine antibody responses.

The team didn’t test whether these antibodies could prevent infection, but it’s significant that these antibodies could be found in the blood, where they could encounter and potentially block HIV.

Bringing the HIV vaccine to humans

The Crotty Lab plans to investigate how it might change the booster shot regimen to make the HIV vaccine even more effective.

“It was incredible to get those results, but of course, we’d like to see a response in 100% of the animals,” says Madden.

Importantly, the antibodies found in the animal subjects resembled the exact kinds of broadly neutralizing antibodies seen in those rare humans who made their own neutralizing antibodies. It’s clear that our immune systems can make these powerful antibodies, given the right training.

“We believe this vaccine approach is even more likely to succeed in humans, because of the immunogenetics,” Crotty says.

The priming immunogen used in this study was evaluated in humans in the HVTN 144 trial and is currently being tested in the Phase 1 trial IAVI G004. IAVI, Scripps Research, the HIV Vaccine Trials Network, and partners are now advancing plans to further evaluate the full immunization regimen in a future human clinical study.

Consumption of ultra-processed food (UPF) results in a distinct metabolic “signature” in the blood, associated with potentially adverse health conditions, suggests a new study by an international team of researchers. The paper, published in Critical Reviews in Food Science and Nutrition, is the first to use targeted metabolomics (the scientific study of the chemical processes involved in cell metabolism) to examine the effects of UPF intake on a large European cohort.

While emerging evidence links consumption of UPF to higher risks of cancer, cardiovascular disease, type 2 diabetes, mortality and obesity, the biological explanations for this remain unclear. To gain insight into the potential metabolic pathways linking UPF to poor health, Dr. Jessica Blanco-Lopez of the International Agency for Research on Cancer (IARC/WHO) and colleagues identified molecular signatures of UPF intake using data from 15,200 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

The team questioned participants about their diet and classified the results using the Nova system, which categorizes foods into four groups, from unprocessed to ultra-processed. The researchers also measured levels of small molecules called metabolites (an intermediate or end product of metabolism) and fatty acids (FAs) in blood samples taken from the participants. Then, they used regression modeling to identify metabolite and FA “signatures” associated with UPF consumption while taking into account demographic, lifestyle and other confounding factors.

UPF intake was found to be associated with 22 circulating metabolites. Higher UPF consumption was associated with higher occurrence of certain lipid derivatives that are biomarkers of impaired fatty acid oxidation and mitochondrial dysfunction, and lower occurrence of several other lipids that are essential for cell membrane stability, permeability and cell signaling. This metabolic signature suggests that UPF consumption may stimulate the synthesis of endogenous lipids (fatty compounds, such as cholesterol) and inhibit healthy lipid processing.

UPF intake was also associated with eight plasma FAs. Higher UPF consumption resulted in a pattern of high stearic acid levels (which indicate high saturated fat intake or metabolic issues) alongside high levels of long-chain polyunsaturated FAs, suggesting the metabolic impact of UPFs extends beyond their fat content to stimulate internal lipid synthesis from excess dietary carbohydrates. This association further confirms that even low levels of industrial fatty exposure persist in circulation.

Blanco-Lopez, whose background is in pediatrics and oncology—which led her to become involved in studies related to nutrition and metabolism—says, “These findings have several implications. The simultaneous decline in protective FA and the increase of metabolic stress suggest that UPF consumption may contribute to health risks through nutritional displacement and inducing metabolic disruption. Our study underscores the potential metabolic impact of UPFs and highlights the need for further research using targeted and untargeted metabolomics approaches to clarify the biological pathways linking food processing with chronic diseases and mortality.”

A limitation of the paper is that this study observed people at one point in time rather than following them over many years. Because of this, the research team cannot definitively say that eating ultra-processed foods causes the metabolic changes they found. They can only show that these two things are associated or linked together.

“We spent considerable time evaluating and refining the analytical approach, testing several different methodologies and strategies throughout the process,” adds Blanco-Lopez. “What was particularly reassuring was that despite these different approaches, the results remained remarkably consistent. This gave us greater confidence in the robustness and reliability of the findings.”

The human brain is known to naturally change with age, shrinking in size and volume after people reach their 30s or 40s. In some cases, however, it can age faster than expected, which can increase the risk of early memory loss, cognitive decline and some brain-related disorders.

Faster brain aging has been linked to various neurological and psychiatric disorders, as well as some neurodegenerative diseases. The factors that influence the speed at which the brain ages, however, have not yet been clearly and comprehensively elucidated.

Researchers at Jilin University and China Medical University recently analyzed available neuroimaging, genomic and biological data to better understand the contribution of metabolic processes (i.e., the chemical reactions that transform food into energy) to brain aging. Their findings, published in Molecular Psychiatry, suggest that higher levels of glucose in the blood are associated with accelerated brain aging.

Uncovering metabolic signatures of brain aging with AI

To explore the biological underpinnings of brain aging, the researchers analyzed data from the UK Biobank, a large biomedical database that contains health-related, genetic and imaging data collected from thousands of people living in the U.K. By analyzing these people’s brain scans, they derived measurable brain features, such as the size of specific brain regions, tissue characteristics and structural changes.

Subsequently, they trained machine learning algorithms to predict the age of people based on the brain features they identified. They found that a specific statistical method, known as a least absolute shrinkage and selection operator (LASSO) regression model, was best at predicting the age of people’s brains, with an average error rate of 3.26 years.

“We integrated multimodal neuroimaging (MRI), plasma metabolomics, and genomic data from the UK Biobank to identify metabolic markers of brain aging and evaluate their causal relevance,” wrote Zhirong Li, Yating Miao and their colleagues in their paper. “Using 1,079 imaging-derived phenotypes (IDPs) from 4,333 healthy participants, we trained and validated machine learning models for brain age prediction, with a LASSO regression model achieving the best performance. Brain age gap (BAG) was then estimated in 37,458 participants.”

Using the best-performing LASSO model, the researchers calculated a value called BAG for thousands of people included in the UK Biobank database. This is essentially a value indicating whether a person’s predicted brain age is higher or lower than their actual age, and by how many years.

Li, Miao and their colleagues then analyzed metabolomics data derived from the same people’s blood samples. This allowed them to identify nine molecules in the blood that appeared to be significantly associated with BAG values.

Notably, glucose appeared to have the strongest association with BAG values. Specifically, higher blood glucose levels were linked to brains that showed more signs of aging in imaging scans and thus appeared older than their actual age.

“Association analyses in 21,780 individuals identified nine plasma metabolites significantly linked to BAG after Bonferroni correction, with glucose showing the strongest effect (β = 0.32, P = 9.90 × 10⁻¹²),” wrote Li, Miao and their colleagues. “Genome-wide association studies (GWAS) identified 392 BAG-associated single-nucleotide polymorphisms (SNPs) (P < 5 × 10⁻⁸), and two-sample Mendelian randomization (MR) provided evidence supporting a potential causal role of glucose in accelerating brain aging.”

Informing the prevention of some brain-related conditions

This study offers evidence suggesting that glucose in the blood may contribute to processes linked to accelerated brain aging. Interestingly, the researchers found that higher levels of blood glucose were also linked to an increased risk of developing seven different conditions known to affect brain function.

“Clinically, elevated plasma glucose was positively associated with seven brain disorders, including all-cause dementia, Alzheimer’s disease, vascular dementia, Parkinson’s disease, stroke, depression, and anxiety, and negatively associated with cognitive performance, movement function, and mental health outcomes,” wrote the authors.

“Higher glucose concentrations were also associated with reduced regional brain volumes across 80 cortical, subcortical, and cerebellar regions. These findings implicate glucose metabolism as a modifiable pathway in brain aging, with implications for early intervention strategies aimed at preserving brain health across the lifespan.”

Future studies could draw inspiration from the team’s findings and further explore the association between higher glucose levels and brain aging, perhaps focusing on specific neurodegenerative or neuropsychiatric conditions. Eventually, the recent work by Li, Miao and their colleagues may contribute to the development of strategies for monitoring and preserving brain health.

Glaucoma is the leading cause of irreversible visual impairment worldwide. Because the disease often progresses without symptoms for years, many patients are diagnosed only after permanent damage to the optic nerve has already occurred. Earlier detection through targeted screening could help prevent vision loss.

A new study based on the FinnGen dataset, which includes hundreds of thousands of Finnish participants and more than 21,000 individuals with glaucoma, demonstrates that genetic information can be used to identify people at particularly high risk of developing the disease. The paper is published in the journal Ophthalmology.

The researchers calculated a polygenic risk score for each participant by combining the effects of numerous genetic variants associated with glaucoma. Based on these scores, the population could be divided into groups with markedly different lifetime risks of developing the disease.

Among individuals whose polygenic risk score ranked in the highest 1% of the population, nearly half developed glaucoma during their lifetime. In contrast, fewer than three out of every 100 individuals in the lowest 1% risk group developed the disease.

The polygenic risk score also predicted disease severity after diagnosis. Patients with a high genetic risk were more likely to require additional medications, laser treatments and glaucoma surgery than those with a low genetic risk.

“Our findings show that genetic risk information can identify individuals at increased risk of glaucoma decades before the disease develops. In the future, this could enable more targeted screening and earlier diagnosis for those who would benefit most,” says ophthalmologist and adjunct professor Joni Turunen from the University of Helsinki, HUS Eye Clinic and the Folkhälsan Research Center.

Toward the use of personalized genetic risk information in health care

Traditionally, inherited susceptibility to glaucoma has been assessed based on family history. However, the study found that polygenic risk scores provide a substantially more accurate estimate of an individual’s genetic risk than information on whether close relatives have developed the disease.

“A polygenic risk score combines the effects of numerous genetic variants across the genome into a single measure of genetic risk. Our study demonstrates that genetic information could significantly complement current methods for risk assessment,” says Nina Mars, one of the senior authors of the study from the Institute for Molecular Medicine Finland (FIMM), University of Helsinki.

“To our knowledge, this is one of the largest studies in the world to evaluate both the association of polygenic risk with glaucoma incidence and disease prognosis within the same dataset. These results provide a strong foundation for incorporating genetic risk information into future screening programs,” says Eemeli Tusa, a medical student and doctoral researcher at the University of Helsinki, who conducted the study.

According to the researchers, the next important step is to investigate in prospective follow-up studies how polygenic risk information can be integrated into routine health care and whether risk-based glaucoma screening is cost-effective.

The research was carried out in collaboration among researchers from the Institute for Molecular Medicine Finland (FIMM) at the University of Helsinki, the Folkhälsan Research Center and the HUS Eye Clinic.

Every few scrolls, another health expert appears on the screen. While some are genuinely qualified, others simply sound convincing enough to pass as one. With AI-generated content flooding feeds, avoiding such advice is becoming increasingly difficult. The way people access health advice has shifted, and for many, social media might be a primary source of information. We need to keep up with its impact because, unlike traditional health channels, these platforms often lack strong editorial checks, making it easier for misinformation to spread.

A recent study surveyed more than 7,000 adults to understand how people in the U.S. use social media for health information. Nearly 80% of users believe that health information on social media is false or misleading.

Yet despite this widespread mistrust, more than 1 in 5 users still report making health-related decisions based on what they see on these platforms. This tendency is more pronounced among adults older than 65 and Hispanic individuals. The health care interaction wasn’t limited to consumption—about 85% of users said they posted or shared personal and general health information on social media.

The findings were published in JAMA.

Closing the old data and new reality gap

The influencer economy is booming, now worth billions, and health care content is emerging as a fast-growing slice of it. The health care social media space alone is valued at about USD 1.27 billion in 2026, with projections climbing to nearly USD 3.8 billion by 2035. As a result, many creators have rushed into health content creation to ride this wave.

The rapid growth has also raised several concerns. There is no consistent screening of social media content by any regulatory body, so misleading information spreads quickly, and biased health advice, often shaped by hidden conflicts of interest, can be shared as genuine advice from a content creator to followers.

The consequences include real-life harm caused by self-diagnosis without proper guidance, or even unnecessary and unproven treatments.

National surveys in the U.S. have found that adults are seeking health information online and on social media. But most of that research predates the AI-driven platforms shaping what we see today.

To bridge the gap between old data and current reality, the researchers analyzed data from the 2024 Health Information National Trends Survey (HINTS), a nationally representative survey that enabled them to examine the habits of 7,278 people who were chosen to represent approximately 262 million adults across the United States.

The researchers didn’t just ask whether people liked social media. They focused on four key behaviors among users: sharing health content, participating in online communities, making health decisions based on what they see, and their perceptions of distrust and misinformation. They also tracked how people with chronic conditions, like cancer, heart disease or mental health issues, used these platforms compared with people without such conditions.

About 88% of U.S. adults used social media, and most of them engaged with health content, with 70% taking part in online health communities. What stood out was the gap between belief and behavior. Even though most users believed health information on social media was false or misleading, many still relied on it when making real health decisions.

People with long-term health conditions used social media at high rates (85.5%) but were less likely to share health information or join online groups. The data also revealed that those with higher education and higher household incomes were more likely to distrust health information on social media.

Social media is no longer a secondary medium; it now plays a major role in how U.S. adults get health information, and the findings make that clear. The researchers observed this among people with and without chronic conditions and called for better ways to ensure that health content is accurate and to push back against AI-amplified misinformation.

For most women, the body begins to change dramatically in their 40s or 50s. This transition, known as menopause, is defined as 12 consecutive months without a menstrual period, marking the end of the reproductive years. While researchers are aware of the functions the ovaries perform during active reproductive years, what happens to the organ after menopause is largely a mystery.

A recent study in Molecular Human Reproduction investigated what happens to the ovary in mice after it stops producing eggs, a period known as the post-reproductive stage, similar to menopause in humans.

Researchers found that even after the ovary can no longer support reproduction, it doesn’t simply become inactive. Instead, aging ovaries undergo remarkable changes, producing a different set of signaling molecules from those of younger ovaries.

In doing so, the ovary shifts away from its reproductive role and transforms into an organ that assumes immune functions, participating in processes such as inflammatory signaling and leukocyte activation.

What comes after eggs?

Ovaries change throughout a woman’s life, from producing immature eggs at birth to releasing mature eggs during the reproductive years, then shrinking in size and function after menopause. Women are born with a fixed, limited supply of follicles—small sacs holding immature eggs—and that supply steadily shrinks with age.

The ovary ages decades before any other organ in the body, showing up as a drop in both the number and quality of follicles. By menopause, only about 1,000 follicles remain.

Due to advances in medical science, humans live much longer than they did a century ago. Yet surprisingly little is known about what the ovaries do after menopause.

Studying human ovaries is challenging because access to samples is limited. To help answer that question, researchers turned to mice, as their ovaries follow a similar pattern of aging: Fertility declines before they enter a post-reproductive stage known as oopause.

To find out how the ovary changes after it can no longer produce eggs, researchers studied mice at different stages of life, creating a timeline of ovarian aging. They selected three groups of mice: reproductively young (2 months old), reproductively old (18 months old) and post-reproductive (24 months old, which is past when they hit oopause).

One ovary from each pair was used to study the physical structure, and the other was used to study its genetic activity via transcriptomics. This allowed researchers to see whether the post-reproductive ovary was still functioning and what its cells were doing. They then used existing data sets to identify which of these active genes produced molecules that could signal to other parts of the body.

An ovary remade by inflammation

They found that by the time mice reached the post-reproductive stage, they had completely run out of follicles, and the ovaries became much stiffer due to a significant increase in collagen. Even after follicle loss leveled off, the ovaries kept changing at the molecular level. Researchers discovered an influx of immune cells in the organ.

The aging ovaries were packed with T cells, macrophages and large giant cells, indicating a shift from a primarily reproductive state to one dominated by the immune system.

While the genes responsible for egg production and reproductive hormone synthesis were mostly turned off, those related to inflammation, immune responses and white blood cell activation were aggressively turned on. They also found that these newly transformed ovaries send out chemical signals that travel through the bloodstream.

The researchers said these findings challenge the idea that the post-reproductive ovary is inactive. Instead, they suggest it takes on an immune-like role, with the potential to influence aging throughout the body through pro-inflammatory signaling.

Future studies confirming similar changes in human ovaries could open the door to new ways to improve the lives of millions of postmenopausal women by targeting ovarian inflammation to reduce the risk of inflammatory and age-related diseases.

A new study led by researchers at The University of Texas MD Anderson Cancer Center has identified a way to tailor drug combinations based on specific tumor biology to improve outcomes for treatment-resistant advanced melanoma.

In preclinical models from patients with treatment-resistant tumors, combining standard BRAF and MEK inhibitors with a drug to block proteins in the BCL2 family—which drive tumor growth—induced tumor regression in a molecularly defined subset of resistant tumors, suggesting a path toward biomarker-guided therapy.

The study, published in Nature Communications, was led by Vashisht Gopal Yennu Nanda, Ph.D., associate professor of Melanoma Medical Oncology and Translational Molecular Pathology, in collaboration with senior author Michael A. Davies, M.D., Ph.D., chair of Melanoma Medical Oncology.

“Targeted therapy works by shutting down the main signal driving melanoma growth, but tumors often have backup systems that keep them alive,” Yennu Nanda said. “By identifying which protein a tumor relies on for survival, we may be able to match patients to drug combinations tailored to their specific tumor biology.”

Resistance points to survival proteins

Approximately half of all melanomas carry a mutation in the BRAF gene, which drives uncontrolled tumor growth. For nearly a decade, the standard of care for these patients has been a combination of BRAF and MEK inhibitors, which initially works for most patients. However, roughly 80% of patients develop acquired resistance and disease progression within two years, potentially due to an increase in certain proteins within the BCL2 family.

Cancer cells often evade therapy by increasing production of “survival proteins” in the BCL2 family—usually BCL2, BCL-xL and MCL1. The researchers confirmed that melanoma tumors express unusually high levels of these proteins compared with most other cancer types and that levels of BCL2 increase in patients following BRAF-MEK inhibitor therapies, likely contributing to treatment resistance.

Different tumors, different vulnerabilities

Using a large collection of patient-derived xenograft (PDX) models established from melanomas with acquired resistance to standard therapy, the researchers tested the addition of a BCL2 inhibitor (navitoclax or venetoclax) to the standard two-drug regimen. They found a subset of previously resistant tumors regressed with the new combination in these models.

Tumors with high baseline levels of BCL2 tended to respond, while tumors with high baseline MCL1 expression tended to resist. To confirm the role of MCL1, the researchers artificially raised its levels in tumor cells, which induced resistance to the triple combination.

For tumors that overproduce MCL1, the team tested an alternative regimen by pairing BRAF-MEK inhibitors with an experimental MCL1 inhibitor called AZD5991. In a high-MCL1 PDX model, this combination produced complete tumor regression, with no detectable tumors at the end of the experiment.

An unexpected cardiac safeguard

MCL1 inhibitors previously have demonstrated antitumor activity but have been associated with heart-related side effects in early clinical trials, leading several studies to be paused or halted. In this study, adding BRAF-MEK inhibitors appeared to protect heart cells from the damaging effects of the MCL1 inhibitor.

In laboratory models, the MCL1 inhibitor alone disrupted cardiac cell energy production and caused signs of damage. Adding BRAF and MEK inhibitors largely reversed these effects, potentially because the MEK inhibitor helped restore energy production in heart cells that MCL1 inhibitors otherwise disrupt. Further research is needed to determine whether this protective effect translates to patients.

“We did not anticipate that pairing these drugs would reduce MCL1 inhibitor toxicity,” Davies said. “If this finding is confirmed in clinical trials, it could give a second life to a class of drugs that has struggled to advance through development. It also reinforces that the most effective combinations are those that eliminate cancer while sparing healthy tissue.”

Clinical trial clues to pursue

These findings support the design of biomarker-guided clinical trials that match patients to drug combinations based on tumor BCL2 and MCL1 expression. To further this research, the team is analyzing samples from a recent randomized Phase 2 clinical trial of dabrafenib, trametinib and navitoclax in BRAF-mutant melanoma patients to determine whether MCL1 expression predicted clinical response.

Additional preclinical and translational studies will be needed to evaluate the safety of BRAF-MEK inhibitor and MCL1 inhibitor combinations before they can be evaluated in patients.

“Patients whose melanoma has stopped responding to standard therapies currently have very few effective treatment options,” Yennu Nanda said. “Our findings could help address this critical need for these patients by guiding clinicians toward combinations tailored to each individual’s tumors.”

For patients struggling to breathe because of acute respiratory failure, clearing mucus from the airways is a routine part of treatment. Mucoactive agents are widely used for this purpose. But after years of clinical use, one question remains: Do mucoactive agents actually help?

To figure this out, researchers designed a large study called the MARCH (Mucoactives in Acute Respiratory Failure: Carbocisteine and Hypertonic Saline) randomized trial, which included nearly 2,000 adults across 71 hospitals in the United Kingdom who were on ventilators and having trouble clearing mucus. The focus of the study was to determine the effectiveness of two widely used mucoactive agents: carbocisteine and hypertonic saline (HTS).

The drugs did not deliver the hoped-for benefits. Those who were on carbocisteine spent about the same amount of time on the ventilator as those who didn’t get any treatment, and the same was true for HTS. Instead, the medications appeared to do more harm than good. Patients treated with these mucoactive agents had side effects like bleeding in the stomach, tightened airways and a drop in blood oxygen levels.

The findings are published in the New England Journal of Medicine.

More harm than good?

We can’t live without breathing, and acute respiratory diseases make that essential function extremely difficult, sometimes impossible. Doctors often have to place such patients in intensive care on a ventilator, which breathes for them. However, being on a ventilator makes it harder for the body to clear mucus from the airways naturally. The mucus also becomes thicker and stickier, so it builds up instead of clearing out.

To overcome this, patients are often given mucoactive agents to loosen or clear mucus. More than 80% of ICUs around the world use these drugs, giving them to roughly 1 in 4 or 5 ventilated patients. However, most doctors administer them based on observation and experience, as there is insufficient evidence to show they actually work. Safety also remained unclear, particularly for routine use in critically ill patients on ventilators.

In this trial, the researchers set out to settle both sides of that question: Do these treatments help patients, or could they actually be causing harm?

They selected participants age 16 or older in intensive care units (ICUs) who were on a breathing machine because of sudden lung failure and had difficulty clearing mucus from their lungs, as determined by their doctors.

They used a 2-by-2 factorial design, splitting participants into four groups to test two treatments simultaneously. The groups included the carbocisteine group, the HTS group, those who received both and those who received neither.

They continued this open-label study, in which doctors and researchers knew who was receiving what, for up to 28 days or until the patient was able to breathe on their own. The team noted how long it took patients to be taken off the ventilator and whether they experienced any complications during the study period.

No gain, clearer risks

Neither carbocisteine nor hypertonic saline made any difference in how long patients stayed on ventilators compared with usual care. In all groups, patients came off ventilation and were holding steady at around 7–8 days.

Patients who received carbocisteine were about seven times more likely to develop serious bleeding in the upper stomach or gut than those who did not (1.4 vs. 0.2%). Patients treated with HTS experienced more breathing-related complications than those in other groups.

They were more likely to develop bronchoconstriction requiring urgent rescue medication, as well as more frequent dangerous drops in blood oxygen levels during treatment. Neither of the mucoactive therapies led to meaningful improvements in survival or other major outcomes, like how long patients stayed in the ICU or hospital.

ICU practice may need revisiting

The researchers noted that the findings point to potential harm from both mucoactive agents, suggesting their routine use in clinical practice should be approached with caution.

Health care systems and hospitals may need to rethink ICU protocols, especially the routine use of carbocisteine and hypertonic saline in ventilated patients, to reduce avoidable side effects. The results call for better monitoring of side effects when mucoactive agents are included in treatment.