Health

Doctors just found a way to slow one of the deadliest prostate cancers

A major international study led by UCL researchers has found that combining two cancer drugs could substantially slow the progression of a severe and often deadly form of prostate cancer in men with specific genetic mutations.

Published in Nature Medicine, the Phase III AMPLITUDE trial tested whether adding niraparib, a targeted cancer therapy known as a PARP inhibitor¹, could enhance the effectiveness of the current standard treatment, abiraterone acetate and prednisone (AAP).²

Targeting Genetic Weaknesses in Prostate Cancer

The study focused on men with advanced prostate cancer that had spread to other parts of the body and who were beginning treatment for the first time. All participants had mutations in genes involved in homologous recombination repair (HRR), a key system that helps repair damaged DNA.

When these DNA repair genes malfunction, cancer cells can multiply and spread more rapidly. About one in four men with advanced prostate cancer at this stage have mutations in HRR-related genes, including BRCA1, BRCA2, CHEK2, and PALB2.

How the Study Was Conducted

Currently, the standard treatment for advanced prostate cancer is AAP (or similar drugs). Roughly one in five patients also receive docetaxel chemotherapy. However, patients with HRR gene mutations typically experience faster disease progression and shorter survival under standard care.

The AMPLITUDE trial, led by Professor Gerhardt Attard of the UCL Cancer Institute, involved 696 men across 32 countries, with a median age of 68. Half received the combination of niraparib and AAP, while the other half received standard AAP treatment with a placebo. More than half of the participants (55.6%) carried mutations in BRCA1 or BRCA2.

The trial was double-blind, meaning neither the patients nor their doctors knew who received the active treatment.

Key Findings from the AMPLITUDE Trial

After a median follow-up period of just over two and a half years (30.8 months), researchers found notable benefits from the drug combination:

Reduced progression risk: Niraparib lowered the risk of cancer growth by 37% in all participants, and by 48% in those with BRCA1 or BRCA2 mutations.
Slower symptom worsening: The time until symptoms worsened was about twice as long for those receiving niraparib. Only 16% of these patients experienced significant symptom progression, compared to 34% in the placebo group.
Potential survival benefit: A trend toward improved overall survival was seen in the niraparib group, though a longer follow-up period is needed to confirm whether it extends life expectancy.

Expert Perspective

Professor Attard said: "Although current standard treatments are very effective for the majority of patients with advanced prostate cancer, a small but very significant proportion of patients have limited benefit. We now know that prostate cancers with alterations in HRR genes account for a significant group of patients whose disease recurs quickly and has an aggressive course. By combining with niraparib we can delay the cancer returning and hopefully significantly prolonging life expectancy.

"These findings are striking because they support widespread genomic testing at diagnosis with use of a targeted treatment for patients who stand to derive the greatest benefit.

"For cancers with a mutation in one of the eligible HRR genes, where niraparib has been approved, a doctor should consider a discussion that balances the risks of side effects against the clear benefit to delaying disease growth and worsening symptoms." ³

Side Effects and Safety

While the treatment was generally well tolerated, side effects were more common in the niraparib group. Significantly more cases of anemia and high blood pressure were reported with niraparib, and 25% of patients required blood transfusions. Treatment-related deaths were also higher in the niraparib group (14 versus 7), though overall discontinuation rates remained low.

The study's authors note that while the results are promising, further research is needed to confirm long-term survival benefits and to explore the impact of newer imaging techniques and broader genetic testing.

Prostate Cancer: Key Statistics

Globally, an estimated 1.5 million men are diagnosed with prostate cancer each year. In the UK prostate cancer is the most common cancer in men, with more than 56,000 men diagnosed every year, and around 12,000 men die from the disease each year.

The AMPLITUDE trial was sponsored by Janssen Research & Development, part of Johnson & Johnson.

Notes

PARP inhibitors, such as niraparib, are a type of targeted therapy that work by blocking the PARP protein, which is involved in repairing damaged DNA in cancer cells. By inhibiting PARP, the cancer cells are unable to repair the DNA damage, leading to their death.
Abiraterone acetate and prednisone (APP) are both hormone therapies. This combination blocks androgen production in the testes, adrenal glands, and the tumor itself, slowing cancer growth by reducing the available testosterone for the cancer cells.
In the UK, Niraparib is approved to treat some types of cancer but has not yet been approved for prostate cancer. The National Institute for Clinical Excellence has said it waiting for further information, before it can make a decision. https://www.nice.org.uk/guidance/ta1032 ^[1]

Staff skipped checks and said a vulnerable young woman was safe. Days later, she was dead

A coroner says some of the care Cerys Lupton-Jones was given at a mental health unit was a "shambles"....

Scientists discover how a high-fat keto diet could keep your brain young

Protecting your brain's energy and keeping your mind sharp might start with what's on your plate. Foods such as fish and seafood, meat, non-starchy vegetables, berries, nuts, seeds, eggs, and even full-fat dairy may play a key role in maintaining cognitive health.

Exploring the Power of the Ketogenic Diet

At the University of Missouri, researchers are exploring how these foods influence brain function. Their work focuses on a high-fat, low-carbohydrate eating plan known as the ketogenic diet. Early results suggest that this approach could not only support long-term brain health but also slow or even prevent cognitive decline, especially among individuals who face a higher genetic risk of developing Alzheimer's disease.

Inside the Roy Blunt NextGen Precision Health building, Ai-Ling Lin, a professor in the School of Medicine, and doctoral student Kira Ivanich are examining how the ketogenic diet may benefit people with the APOE4 gene, which is the strongest known genetic risk factor for late-onset Alzheimer's disease.

In their recent study using mice, Lin and Ivanich found that females with the APOE4 gene developed healthier gut bacteria and showed higher brain energy levels when following a ketogenic diet compared to those on a high-carbohydrate diet. Males did not show the same improvement, suggesting that gender may influence who benefits most from this dietary approach.

How the Brain Uses Fuel

The key lies in how the brain produces its energy.

"When we eat carbs, our brains convert the glucose into fuel for our brains, but those with the APOE4 gene -- particularly females -- struggle to convert the glucose into brain energy, and this can lead to cognitive decline down the road," Ivanich said. "By switching to a keto diet, ketones are produced and used as an alternative fuel source. This may decrease the chance of developing Alzheimer's by preserving the health of brain cells."

These findings highlight the potential of "precision nutrition," an approach that adapts diets and interventions to fit a person's unique biology.

"Instead of expecting one solution to work for everyone, it might be better to consider a variety of factors, including someone's genotype, gut microbiome, gender and age," Lin said. "Since the symptoms of Alzheimer's -- which tend to be irreversible once they start -- usually appear after age 65, the time to be thinking about preserving brain health is well before then, so hopefully our research can offer hope to many people through early interventions."

Advancing Research Through Collaboration

Lin joined Mizzou in part for its collaborative environment and advanced imaging facilities located in the NextGen Precision Health building and at the University of Missouri Research Reactor.

"We can do a lot of things in-house here that at other places we would have to outsource," Lin said. "This is team science. The impact we make will be much better when we work together than by ourselves."

With cutting-edge imaging equipment and both research and clinical spaces under the same roof, the NextGen Precision Health building allows Mizzou to move quickly from preclinical models to human trials.

For Ivanich, that real-world impact is personal.

"When my grandmother got Alzheimer's, that sparked my interest in this topic, so being able to make an impact to help people preserve their brain health is very rewarding," she said. "With Mizzou being a leading research university and having a tight-knit community feel, I know I'm at the right place."

"Ketogenic diet modulates gut microbiota-brain metabolite axis in a sex-and genotype-specific manner in APOE4 mice" was published in the Journal of Neurochemistry.

This simple innovation could change blood pressure testing forever

A newly developed method that improves the accuracy of ankle blood pressure measurements could transform care for people who are unable to have their blood pressure taken from the arm.

Researchers from the University of Exeter Medical School, in a study published in BMJ Open and funded by the National Institute for Health and Care Research (NIHR), analyzed data from more than 33,000 individuals to create a personalized predictive model. This model enables healthcare professionals to estimate arm blood pressure more precisely using ankle readings (when compared with earlier approaches). To make the process easier to use, the team has also launched an online calculator that helps both clinicians and patients interpret ankle-based results.

Why Accuracy in Blood Pressure Measurement Matters

More than one billion people worldwide live with high blood pressure, a major risk factor for heart disease, stroke, and kidney problems. Reliable measurements are crucial for diagnosing and managing the condition effectively.

Although blood pressure is typically measured on the upper arm, some people cannot have it taken there due to disability, limb loss, or conditions such as stroke. In such cases, readings are taken from the ankle. However, ankle measurements are usually higher than arm readings, and because treatment guidelines are based on arm data, this difference can lead to inaccurate diagnoses and inappropriate treatment decisions.

Improving Accuracy and Reducing Misdiagnoses

Professor Chris Clark, who led the research, explained: "Our new method will give a more accurate blood pressure reading for around two percent more people. This doesn't sound a big number but remember, around a third of adults have high blood pressure and once you get into your 60s it's more than half of the adults. The NHS Health Check Programme diagnoses 38,000 new cases annually in England alone, so two percent equates to 750 fewer potential misdiagnoses per year in England, and tens of thousands globally."

To achieve this, the researchers used statistical modeling on data from 33,710 people (mean age 58 years, 45 per cent female) across multiple countries. The analysis explored the relationship between arm and ankle blood pressures, developed a predictive equation for estimating arm values from ankle readings, and examined how ankle readings relate to important health outcomes (such as heart attack risk).

This advancement could help close a significant health gap by providing accurate and personalized blood pressure results for people who have been excluded from standard monitoring. It is estimated that up to 10,000 adults in the UK live with upper limb loss, while 75 per cent of the country's 1.3 million stroke survivors experience upper limb difficulties that can make arm-based measurements challenging or impossible.

The project received support from the Stroke Association and the Thalidomide Trust, two organizations advocating for people affected by these conditions.

Expert Reactions and Public Health Impact

Juliet Bouverie OBE, CEO of the Stroke Association, said: "Someone in the UK has a stroke every five minutes, with high blood pressure accounting for around half of those. Around two-thirds of stroke survivors will leave hospital with some form of disability, including paralysis in an arm, which can prevent getting accurate blood pressure readings from the affected limb. Many stroke survivors feel anxious about having another stroke, so receiving an accurate blood pressure reading in the ankle will not only provide benefits in the primary prevention of stroke, but importantly in easing the minds of stroke survivors who are already dealing with the devastating impact of stroke."

Professor Kevin Munro, Director of NIHR's Research for Patient Benefit Programme, said: "This research has identified an ingenious solution to an important problem -- finding a way to measure blood pressure for people who cannot have it monitored via the upper arm. Keeping track of blood pressure is a vital tool to help keep people healthy and this NIHR-funded research will help to spot high blood pressure and treat it even more widely."

The paper titled "Arm Based on LEg blood pressures (ABLE-BP): Can systolic ankle blood pressure measurements predict systolic arm blood pressure? An individual participant data meta-analysis from the INTERPRESS-IPD Collaboration" is published in BMJ Open.

The online calculator is available at: ABLE-BP Tool -- https://ablebp.research.exeter.ac.uk/^[1]

"Why should I not be able to have my blood pressure taken?"

TV presenter Sue Kent, 62 from Swansea, has an upper limb disability caused by the drug Thalidomide, which was prescribed to her mother during pregnancy. She has eight-inch arms which aren't big enough for blood pressure to be taken.

Sue said: "I rarely had my blood pressure taken when I was younger, but when I did, I used to have a really big cuff they would put around my thigh and take the blood pressure there. Whether it was accurate or not nobody worried, but I didn't seem to have blood pressure problems.

"But then I had a cataract operation, and somebody took my blood pressure from my ankle, and it was very high. They did it three times and every time it was high, and it made me very worried. They (medical staff) weren't worried and carried on and did the cataract operation, but I was quite distressed."

Sue was diagnosed with Meniere's disease in 2017, which is a rare inner ear condition which has left her partially deaf.

She said: "I was worried I was going to have a stroke because Meniere's can be an indicator the blood flow isn't going to the brain. I knew I couldn't have my blood pressure taken accurately, so I went privately to have dye injected to check everything was OK.

"As you get older blood pressure is an important indicator of so many things, including things that could be seriously wrong. Prodding about in the dark and guessing isn't really a safe thing to do. You need the right information about your blood pressure."

Sue hopes this new method could potentially help her and thousands of others like her have something most of us take for granted -- an accurate blood pressure reading.

She said: "Why should I not be able to have my blood pressure taken when it's available to most people and is a relatively simple thing to do?

"When you're disabled, you're more likely to die younger for a variety of reasons, so this resource tips the scales a bit more in our favor. This could put us on a level playing field with everybody else when it comes to blood pressure. It means reassurance and maybe an early diagnosis if something is wrong."

Sidebar

Magazine menu