While breast cancer survival continues to improve, thanks to advances in detection and treatment, when breast cancer relapses — or returns after initial treatment — it is still incurable. For the 30 percent of women and men who do relapse, the only option is continuous and indefinite treatment which cannot eliminate the cancer completely. Some breast cancers, like triple negative and HER2+, recur within a few years, and others like ER+ can recur decades later. Until now, there has not been a way to identify those breast cancer survivors who harbor the dormant cells that lead to recurrence in real time and to intervene with a treatment that can prevent incurable relapse.

In a randomized phase II clinical trial with 51 breast cancer survivors, existing drugs were able to clear dormant tumor cells from 80 percent of the study participants. The three-year survival rate without any disease recurrence was above 90 percent in patients who received one drug and 100 percent for patients who received both study drugs.

“The lingering fear of cancer returning is something that hangs over many breast cancer survivors after they celebrate the end of treatment,” said principal investigator Angela DeMichele, MD, MSCE, FASCO, the Mariann T. and Robert J. MacDonald Professor in Breast Cancer Research. “Right now, we just don’t know when or if someone’s cancer will come back — that’s the problem we set out to solve. Our study shows that preventing recurrence by monitoring and targeting dormant tumor cells is a strategy that holds real promise, and I hope it ignites more research in this area.”

Seizing a window of opportunity to wipe out cancer while it’s sleeping

The study builds on previous research that showed how dormant tumor cells continue to lay in wait in some patients after breast cancer treatment. These so-called “sleeper cells,” also referred to as minimal residual disease (MRD), can reactivate years or even decades later. Because they are not “active” cancer cells and can be scattered throughout the body, they do not show up on standard imaging tests that are used to watch for breast cancer recurrence.

Once the sleeper cells begin to expand and circulate in the bloodstream, it can lead to the spread of metastatic breast cancer. Patients who have MRD are more likely to experience breast cancer recurrence and have decreased overall survival.

Lewis Chodosh, MD, PhD, chair of Cancer Biology and senior author of the study, previously led research to identify the pathways that allow dormant tumor cells to survive in patients for decades.

“Our research shows that this sleeper phase represents an opportunity to intervene and eradicate the dormant tumor cells before they have the chance to come back as aggressive, metastatic disease,” Chodosh said. “Surprisingly, we’ve found that certain drugs that don’t work against actively growing cancers can be very effective against these sleeper cells. This tells us that the biology of dormant tumor cells is very different from active cancer cells.”

In the preclinical part of the latest research publication, Chodosh’s team conducted a series of experiments in mice to better understand the underlying mechanisms. They showed that two different drugs — approved by the FDA to treat other conditions — could effectively clear MRD in mice, resulting in longer survival without cancer recurrence. The drugs target autophagy and mTOR signaling, which the researchers found were key mechanisms to allow the tumor cells to remain dormant.

Translating science into original clinical trials

DeMichele’s team first enrolled breast cancer survivors who had completed treatment within the last five years and had clear scans into a screening study that looked for dormant tumor cells in participant’s bone marrow.

If dormant tumor cells were found, patients were then eligible to enroll in the Phase II CLEVER clinical trial, which randomized patients to receive six cycles of either monotherapy with one of two study drugs, or combination therapy with both drugs. The treatment cleared dormant tumor cells in most patients after six to 12 months. After a median follow-up time of 42 months, only two patients on the study have experienced a cancer recurrence.

“We want to be able to give patients a better option than ‘wait and see’ after they complete breast cancer treatment,” DeMichele said. “We’re encouraged by these results that we’re on the right track.”

The team is already enrolling patients in two larger, ongoing studies to confirm and extend the results of the CLEVER study: the Phase II ABBY clinical trial and the Phase II PALAVY clinical trial, available at several cancer centers across the country. Patients interested in learning more about these or other breast cancer clinical trials at Penn Medicine should contact [email protected].

The research was made possible with funding from the National Cancer Institute (R01CA208273) and Department of Defense (BC160784), with additional support from the V Foundation, Breast Cancer Research Foundation, QVC “Shoes on Sale,” Avon Foundation, Raynier Institute & Foundation, and generous philanthropic donations. DeMichele previously reported interim outcomes data from the study at the European Society for Medical Oncology (ESMO) Congress 2023.

Now Tufts researchers led by Krishna Kumar, Robinson Professor of Chemistry, have designed a new, next-generation compound with hopes that it could be more effective with fewer side effects, which they report in a paper in the Journal of the American Chemical Society.

While weight loss drugs currently on the market and in development target one, two, or even three hormone receptors related to glucose metabolism and the desire to eat, the Tufts team has identified a fourth target that could potentially further enhance the control strategy.

“Obesity is linked to over 180 different disease conditions, including cancer, cardiovascular disease, osteoarthritis, liver disease, and type 2 diabetes, and affects over 650 million people worldwide,” said Kumar. “What drives us is the idea that we can design a single drug to treat obesity and simultaneously mitigate the risk of developing a long list of health problems plaguing society.”

How the Drugs Work

After we eat a meal, our gut and brain trigger a hormonal “fuel gauge” that regulates levels of glucose and tells us when we have had enough to eat.

The hormone glucagon-like peptide 1 (GLP-1) is released to help stimulate the production of insulin and the uptake of glucose in muscle and other tissues. With the cells now loaded with fuel, the level of glucose in the blood returns to normal. Ozempic uses GLP-1 with slight modifications to increase its availability in the bloodstream. Its success in controlling blood glucose has prompted the American Diabetes Association to recommend it and other GLP-1-based drugs as the new first line injectable treatments for diabetes, ahead of insulin.

But GLP-1 also acts directly on the brain, making us feel full after having a meal, and it slows down the rate that the stomach contents are emptied into the intestines, creating a more evenly paced release of nutrients and glucose into the bloodstream. That’s why it has also become extremely popular as a weight loss treatment.

It’s still not a perfect drug strategy for weight loss, though. “The biggest problem with GLP-1 drugs is that they have to be injected once a week, and they can induce a very strong feeling of nausea,” said Kumar. “As much as 40% of people using these drugs give up after the first month.”

A second hormone released after eating is glucose-dependent insulinotropic peptide (GIP). It also makes us feel full after a meal. GIP looks a lot like GLP-1, so rather than administer two drugs, researchers created one peptide that incorporates structural elements of both — what’s called in drug development a chimera. That drug, called Mounjaro or Zepbound (the brand names for tirzepatide), has the added benefit of significantly reducing nausea. As a more tolerable treatment, it may overtake Ozempic in the weight loss market.

“And then there is a third hormone, glucagon,” said Kumar. “Paradoxically, it actually increases blood glucose, but at the same time increases the expenditure of energy in cells of the body, raises body temperature, and suppresses appetite.” By adding glucagon to the mix, GLP-1 and GIP end up neutralizing its glucose-enhancing effect, leaving the remaining functionalities of all three hormones working together to enhance weight loss.

Glucagon is also similar in structure to GLP-1 and GIP, so drug developers created a single chimera peptide that incorporates elements of all three hormones, which can be recognized by their three separate receptors. That drug, called retatrudide, is currently in clinical trials that indicate even greater achievable weight loss (up to 24%) compared to the original GLP-1 drugs (6-15%).

Going for the Weight Loss Gold Standard with a Fourth Target

“The goal that people are trying to shoot for is bariatric surgery,” said Kumar. That’s a surgical procedure significantly reducing the size of the stomach, which can achieve long-lasting weight loss up to 30%. “For individuals with persistent obesity and potential deadly associated conditions, it becomes a necessary but invasive treatment.”

Current injectable weight loss drugs still fall short of that gold standard, so the Tufts chemists are focused on a drug redesign that could match the 30% weight loss outcome.

“There is one more hormone we wanted to bring in to complete a weight control quartet,” said Tristan Dinsmore, a graduate student in the Kumar lab and the lead author of the study. “It’s called peptide YY (PYY). This molecule is also secreted by the gut after we eat a meal, and its job is to reduce appetite and slow the process of emptying food from the stomach, but via different mechanisms than either GLP-1 or GIP. It may also be involved in directly ‘burning off’ fat.”

PYY is from a separate and structurally unrelated class of hormones than the first three, so blending its structure into a chimeric peptide that also mimics GLP-1, GIP, and glucagon was not easy. Instead, the Tufts team was able to join two peptide segments end-to-end, creating a new ‘tetra-functional’ clinical candidate.

“One of the limitations of the current drugs is that individual variation, possibly including how people express target receptors or respond to their corresponding hormones, can lead to lesser than desired weight loss outcomes in many patients,” said Martin Beinborn, visiting scholar in the Department of Chemistry. “By hitting four different hormone receptors at the same time, we hope to improve the chances of averaging out such variation toward the goal of achieving greater and more consistent overall effectiveness.”

“A second issue is that patients tend to regain weight after discontinuing currently available GLP-1 related drugs,” said Beinborn, who notes that lifestyle changes should ideally be a complement to medication treatment. This two-pronged approach will not only support reaching and keeping one’s target weight, but may also help preserve bone and muscle mass.

“Recent studies indicate that weight rebound after drug discontinuation is delayed with the newer, more effective GLP-1 mimetics,” he said. “Extending from this observation, one may speculate that multi-chimeras along the lines of the one we discovered could get us closer to the bariatric surgery standard of lasting weight loss.”

The researchers come to the conclusion that these olfactory dysfunctions arise because immune cells of the brain called “microglia” remove connections between two brain regions, namely the olfactory bulb and the locus coeruleus. The olfactory bulb, located in the forebrain, analyzes sensory information from the nose’s scent receptors. The locus coeruleus, a region of the brainstem, influences this processing by means of long nerve fibers originating from neurons in the locus coeruleus and extending all the way to the olfactory bulb. “The locus coeruleus regulates a variety physiological mechanisms. These include, for example, cerebral blood flow, sleep-wake cycles, and sensory processing. The latter applies, in particular, also to the sense of smell,” says Dr. Lars Paeger, a scientist at DZNE and LMU. “Our study suggests that in early Alzheimer’s disease, changes occur in the nerve fibers linking the locus coeruleus to the olfactory bulb. These alterations signal to the microglia that affected fibers are defective or superfluous. Consequently, the microglia break them down.”

Alterations in the membrane

Specifically, the team of Dr. Lars Paeger and Prof. Dr. Jochen Herms, who is a co-author of the current publication, found evidence of changes in the composition of the membranes of the affected nerve fibers: Phosphatidylserine, a fatty acid that usually occurs inside a neuron’s membrane, had been moved to the outside. “Presence of phosphatidylserine at the outer site of the cell membrane is known to be an “eat-me” signal for microglia. In the olfactory bulb, this is usually associated with a process called synaptic pruning, which serves to remove unnecessary or dysfunctional neuronal connections,” explains Paeger. “In our situation, we assume that the shift in membrane composition is triggered by hyperactivity of the affected neurons due to Alzheimer’s disease. That is, these neurons exhibit abnormal firing.”

A wide range of data

The findings of Paeger and colleagues are based on a plethora of observations. These include studies on mice with features of Alzheimer’s disease, analysis of brain samples from deceased Alzheimer’s patients, and positron emission tomography (PET) scans of the brains of individuals with Alzheimer’s or mild cognitive impairment. “Smell issues in Alzheimer’s disease and damage to the associated nerves have been discussed for some time. However, the causes were unclear until yet. Now, our findings point to an immunological mechanism as cause for such dysfunctions – and, in particular, that such events already arise in the early stages of Alzheimer’s disease,” says Joachim Herms, a research group leader at DZNE and LMU as well as a member of the Munich-based “SyNergy” Cluster of Excellence.

Perspectives for early diagnosis

So-called amyloid-beta antibodies have recently become available for the treatment of Alzheimer’s. For this novel therapy to be effective, it needs to be applied at an early stage of the disease, and this is precisely where the current research could be significant. “Our findings could pave the way for the early identification of patients at risk of developing Alzheimer’s, enabling them to undergo comprehensive testing to confirm the diagnosis before cognitive problems arise. This would allow earlier intervention with amyloid-beta antibodies, increasing the probability of a positive response,” says Herms.

RSV causes substantial seasonal illness during fall and winter in the U.S., with an estimated 100,000-150,000 hospitalizations and 4,000-8,000 deaths occurring annually among adults 60 or older.

The results reinforce the recommendations for RSV vaccines in older adults and lay the groundwork for understanding how long a single dose of the vaccine may be effective, according to Wesley Self, MD, MPH, principal investigator for the IVY Network and Senior Vice President for Clinical Research at Vanderbilt University Medical Center.

“These results clearly demonstrate that the RSV vaccines prevent hospitalizations and critical illness due to RSV infection among older Americans,” Self said. “It is exciting to see the public health benefits of this new vaccination program.”

Investigators used data from a multicenter hospital network known as the IVY Network (The Investigating Respiratory Viruses in the Acutely Ill Network) to assess RSV vaccine effectiveness. They used a test-negative, case-control study design among 6,958 persons 60 years or older who had been hospitalized with acute respiratory illness at one of 26 hospitals in 20 US states during two RSV seasons from October 1, 2023-March 31, 2024 and October 1, 2024-April 30, 2025.

Overall, vaccination reduced the risk of RSV hospitalization by 58% during two RSV seasons, including 69% in the first year after vaccination and 48% in the second year after vaccination.

“Our data show that the beneficial effects of RSV vaccines appear to wane over time,” Self said. “Redosing the vaccine at some interval after the initial dose could be a strategy to maintain protection over longer periods of time. It will be important to continue to closely monitor vaccine effectiveness over time to understand how long the benefit lasts after a single dose and if repeat dosing should be considered.”

Current RSV vaccine recommendations are for all adults aged 75 years and older and those aged 60-74 years who are at an increased risk of severe RSV.

This study was funded by the U.S. Centers for Disease Control and Prevention (CDC) via award 75D30122C14944.

In 2009, NASA’s Chandra X-ray Observatory released a captivating image: a pulsar and its surrounding nebula that is shaped like a hand.

Since then, astronomers have used Chandra and other telescopes to continue to observe this object. Now, new radio data from the Australia Telescope Compact Array (ATCA), has been combined with Chandra’s X-ray data to provide a fresh view of this exploded star and its environment, to help understand its peculiar properties and shape.

At the center of this new image lies the pulsar B1509-58, a rapidly spinning neutron star that is only about 12 miles in diameter. This tiny object is responsible for producing an intricate nebula (called MSH 15-52) that spans over 150 light-years, or about 900 trillion miles. The nebula, which is produced by energetic particles, resembles a human hand with a palm and extended fingers pointing to the upper right in X-rays.

The collapse of a massive star created the pulsar when much of the star crashed inward once it burned through its sustainable nuclear fuel. An ensuing explosion sent the star’s outer layers outward into space as a supernova.

The pulsar spins around almost seven times every second and has a strong magnetic field, about 15 trillion times stronger than the Earth’s. The rapid rotation and strong magnetic field make B1509-58 one of the most powerful electromagnetic generators in the Galaxy, enabling it to drive an energetic wind of electrons and other particles away from the pulsar, creating the nebula.

In this new composite image, the ATCA radio data (represented in red) has been combined with X-rays from Chandra (shown in blue, orange and yellow), along with an optical image of hydrogen gas (gold). The areas of overlap between the X-ray and radio data in MSH 15-52 show as purple. The optical image shows stars in the field of view along with parts of the supernova’s debris, the supernova remnant RCW 89.

Radio data from ATCA now reveals complex filaments that are aligned with the directions of the nebula’s magnetic field, shown by the short, straight, white lines in a supplementary image. These filaments could result from the collision of the pulsar’s particle wind with the supernova’s debris.

By comparing the radio and X-ray data, researchers identified key differences between the sources of the two types of light. In particular, some prominent X-ray features, including the jet towards the bottom of the image and the inner parts of the three “fingers” towards the top, are not detected in radio waves. This suggests that highly energetic particles are leaking out from a shock wave — similar to a supersonic plane’s sonic boom — near the pulsar and moving along magnetic field lines to create the fingers.

The radio data also shows that RCW 89’s structure is different from typical young supernova remnants. Much of the radio emission is patchy and closely matches clumps of X-ray and optical emission. It also extends well beyond the X-ray emission. All of these characteristics support the idea that RCW 89 is colliding with a dense cloud of nearby hydrogen gas.

However, the researchers do not fully understand all that the data is showing them. One area that is perplexing is the sharp boundary of X-ray emission in the upper right of the image that seems to be the blast wave from the supernova — see the labeled feature. Supernova blast waves are usually bright in radio waves for young supernova remnants like RCW 89, so it is surprising to researchers that there is no radio signal at the X-ray boundary.

MSH 15-52 and RCW 89 show many unique features not found in other young sources. There are, however, still many open questions regarding the formation and evolution of these structures. Further work is needed to provide better understanding of the complex interplay between the pulsar wind and the supernova debris.

A paper describing this work, led by Shumeng Zhang of the University of Hong Kong, with co-authors Stephen C.Y. Ng of the University of Hong Kong and Niccolo’ Bucciantini of the Italian National Institute for Astrophysics, has been published in The Astrophysical Journal.

NASA’s Marshall Space Flight Center in Huntsville, Alabama, manages the Chandra program. The Smithsonian Astrophysical Observatory’s Chandra X-ray Center controls science operations from Cambridge, Massachusetts, and flight operations from Burlington, Massachusetts.

Globally around 1.3 billion people have high blood pressure (hypertension), and in around half of cases the condition is uncontrolled or treatment resistant. These individuals face a much greater risk of heart attack, stroke, kidney disease, and early death. In the UK the number of people with hypertension is around 14 million.

The international BaxHTN trial, led by Professor Bryan Williams (UCL Institute of Cardiovascular Science) and sponsored by AstraZeneca, assessed the new drug baxdrostat – which is taken as a tablet – with participation from nearly 800 patients across 214 clinics worldwide.

The study was supported by the NIHR Biomedical Research Centre at UCLH.

Results were presented on August 30^th at the European Society of Cardiology (ESC) Congress 2025 in Madrid and are being simultaneously published in the New England Journal of Medicine.

The trial results showed that, after 12 weeks, patients taking baxdrostat (1 mg or 2 mg once daily in pill form) saw their blood pressure fall by around 9-10 mmHg more than placebo – a reduction large enough to cut cardiovascular risk. About 4 in 10 patients reached healthy blood pressure levels, compared with fewer than 2 in 10 on placebo.

Principal Investigator, Professor Williams, who is presenting the results at ESC, said: “Achieving a nearly 10 mmHg reduction in systolic blood pressure with baxdrostat in the BaxHTN Phase III trial is exciting, as this level of reduction is linked to substantially lower risk of heart attack, stroke, heart failure and kidney disease.”

How baxdrostat works

Blood pressure is strongly influenced by a hormone called aldosterone, which helps the kidneys regulate salt and water balance.

Some people produce too much aldosterone, causing the body to hold onto salt and water. This aldosterone dysregulation pushes blood pressure up and makes it very difficult to control.

Addressing aldosterone dysregulation has been a key effort in research over many decades, but it has been so far difficult to achieve.

Baxdrostat works by blocking aldosterone production, directly addressing this driver of high blood pressure (hypertension).

Professor Williams, Chair of Medicine at UCL, said: “These findings are an important advance in treatment and in our understanding of the cause of difficult to control blood pressure.

“Around half of people treated for hypertension do not have it controlled, however this is a conservative estimate and the number is likely higher, especially as the target blood pressure we try to reach is now much lower than it was previously.*

“In patients with uncontrolled or resistant hypertension, the addition of baxdrostat 1mg or 2mg once daily to background antihypertensive therapy led to clinically meaningful reductions in systolic blood pressure, which persisted up to 32 weeks with no unanticipated safety findings.

“This suggests that aldosterone is playing an important role in causing difficult to control blood pressure in millions of patients and offers hope for more effective treatment in the future.”

Historically higher income Western countries were reported to have far higher levels of hypertension; however, largely due to changing diets (adding less salt to food), the numbers of people living with the condition is now far higher in Eastern and lower income countries. More than half of those affected live in Asia, including 226 million people in China and 199 million in India**.

Professor Williams added: “The results suggest that this drug could potentially help up to half a billion people globally – and as many as 10 million people in the UK alone, especially at the new target level for optimal blood pressure control.”

*The ESC 2024 hypertension guidelines recommended a target blood pressure of less than 130/80 mmHg. Prior to 2024 the target had been 140/90 mmHg.

** Figures from Blood Pressure UK