Category: Cancer

False Mechanism in Cancer Trial Drug Raise Concerns for Clinical Research

Cancer drug entered clinical trials based on a false mechanism, exposing risks and costs of testing drugs without knowing their true target.

Photo by National Cancer Institute on Unsplash

A cancer drug currently being tested in patients may have entered clinical trials based on an incorrect understanding of how it works, according to a new study led by the University of Sydney in collaboration with Goethe University, Oxford University and the Institute of Cancer Research, London. 

Published in Nature Chemical Biology, the study found the experimental drug zavondemstat and a closely related research compound, QC6352 – developed to treat cancers such as colorectal, pancreatic and prostate cancer – do not primarily target KDM4, a family of proteins which can help cancer cells grow and spread when it becomes overactive. Instead, both compounds largely work by blocking DHODH, an enzyme cancer cells rely on to produce the molecules needed for rapid growth.

Lead author Professor Lenka Munoz from the University of Sydney School of Medical Sciences and Charles Perkins Centre said: “We can think of DHODH as a machine producing bricks needed to build new DNA. If you switch off the machine, the cell starts running out of bricks and can no longer efficiently copy its DNA and keep dividing.”

These findings could affect the interpretation of previous studies around the world that used the research compound (QC6352) to investigate the biology of the cancer protein and may have implications for the ongoing clinical development of the zavondemstat drug. 

The discovery emerged from research investigating whether zavondemstat and QC6352 could be repurposed for glioblastoma, the most common and aggressive form of brain cancer. 

“We tested these compounds to investigate whether they could potentially be repurposed for glioblastoma treatment,” Professor Munoz said.

“When we tested other KDM4 inhibitors, we found they did not reproduce the anti-cancer effects observed with QC6352. 

“If blocking KDM4 was driving those effects, we would have expected the other inhibitors to behave similarly. Instead, the results suggested QC6352 was acting through a different mechanism.”

“Our study shows this is not just a historical problem but one still happening today. Greater rigour is needed to ensure we understand exactly how potential treatments work before they move into clinical testing.”

Professor Lenka Munoz
Charles Perkins Centre

Using patient-derived glioblastoma stem cells, tumour models and a series of genetic, mechanistic and molecular experiments, the researchers traced the compounds’ response to DHODH rather than KDM4.

“Researchers around the world have used QC6352 as a leading tool to study KDM4 biology, while the related drug zavondemstat progressed into clinical trials based on the same understanding,” Professor Munoz said.

“Our study found much of the anti-cancer activity of these compounds is driven by blocking DHODH rather than KDM4.”

Study highlights broader issue facing cancer drug development

Professor Munoz said the findings highlight a broader challenge in cancer drug development.

“Getting a drug’s mechanism wrong can lead to poorly designed clinical trials, inappropriate patient selection and years of research focused on the wrong biological target,” she said.

“There are well-known examples of cancer drugs advancing through large clinical trials before researchers realised they were not working through the mechanism originally proposed. 

“Our study shows this is not just a historical problem but one still happening today. Greater rigour is needed to ensure we understand exactly how potential treatments work before they move into clinical testing.

“Establishing a drug’s true mechanism early can protect patients, prevent wasted research effort and help ensure what limited funding we have is directed towards genuinely promising treatments.”

The findings also point to DHODH inhibition as a potential new avenue for glioblastoma treatment. Several drugs targeting DHODH are already being investigated for other cancers, raising the possibility they could eventually be tested in patients with brain cancer.       

Beyond identifying the drug’s true target, the researchers developed new compounds that inhibit KDM4 without affecting DHODH, which could help scientists study the role of KDM4 more accurately in future cancer research. 

Source: University of Sydney

Less than a month to go. ONE SMALL SPEEDO. ONE IMPORTANT CAUSE

Excitement builds ahead of the 2026 Hollard Daredevil Run

The countdown is officially on! There are only a few weeks to go until streets around Mzansi are awash with purple, and the excitement is mounting. Friday 23 October sees the 2026 Hollard Daredevil Run take place at Zoo Lake in Johannesburg and at various locations countrywide. 

This annual initiative, which this year carries the bold tagline “Lekker Balls. Lekker Life”, raises much-needed awareness about prostate and testicular cancers and reinforces the potentially life-saving importance of early detection. Over the last seventeen years, the support from Daredevils across South Africa, and beyond, has been nothing short of incredible. It is also the sense of brotherhood and shared purpose that keeps Daredevils coming back. 

The Hollard Daredevil Run is highly visible, with participants running 5km in a purple speedo, but its real purpose is getting South African men and their families talking about prostate and testicular cancers, understanding their risks and taking action through early detection.

“We know that thousands of men running in purple speedos gets people’s attention. What matters is what we do with that attention,” says Adél Kriel, Hollard South Africa’s Head of Experiential Marketing. “There is bravery in putting on a purple speedo in public, but behind this bold campaign is a very serious message: Know your risks, know your body and don’t put off getting checked. It could save your life.”

The more men who participate, the greater the funds raised for CANSA and the Prostate Cancer Foundation (PCF) to fund awareness campaigns, Prostate-Specific Antigen (PSA) screening and patient support. 

The 2026 Hollard Daredevil Run takes place at Zoo Lake in Johannesburg on Friday, 23 October at 15:00, with runs happening at various locations across the country on the same day. Details of run locations around the country will be shared on the Daredevil Run social media platforms.

Purple speedos are being snapped up fast, but there’s still time to secure your entry. Get your colleagues, friends, fellow students and family members to participate in the run as well as raising funds, and start a conversation about men’s health. After all, the Hollard Daredevil Run has always been about much more than the finish line.​

“This October, purple is more than a colour. It’s a conversation starter, but its real impact comes when that conversation extends beyond race day into families, workplaces and communities. The more people who take part, the further that message can reach,” says Kriel. “You don’t have to be a runner. You just have to be willing to show up for this important cause”.

Make a bold decision to make a difference by entering today at https://www.hollard.co.za/daredevilrun. Let’s make this year’s run the most impactful one yet.​

About Hollard  

The Hollard Insurance Group (“Hollard”) is South Africa’s largest privately owned insurance group. Hollard provides short-term, life insurance and investment products to a diverse customer base. Hollard through Hollard International has access to 10 markets across the continent namely South Africa, Botswana, Ghana, Lesotho, Mozambique, Namibia, Zambia, Kenya, Tanzania and Uganda.    

Pneumonia can Reveal Undiagnosed Blood Cancer

Photo by engin akyurt on Unsplash

Severe pneumococcal disease requiring hospitalisation, most commonly pneumonia, can be a sign of previously undiagnosed blood cancer and immunodeficiency in adult patients, according to a study from the University of Gothenburg.

The study followed 156 individuals who developed invasive pneumococcal disease and required hospital care in the Region Västra Götaland between 2018 and 2023. The median age of the patients was 70 years.

The researchers examined the patients’ immune system by measuring antibody levels and studied the presence of M protein, known as a risk marker for blood cancer. The control group consisted of 64 individuals matched for age and sex who did not have invasive pneumococcal disease.

In the pneumococcal disease group, one in four individuals had M protein in their blood, a marker that may be present in blood cancer or in precursor conditions. The examinations led to seven patients being diagnosed with blood cancer, while another twelve were diagnosed with a condition that can, in some cases, progress to blood cancer.

Routine screening should be considered

Eight patients were found to have immunodeficiency, seven of whom were able to start preventive treatment against new, severe infections. These findings were considerably less common in the control group.

The results, published in the journal Scientific Reports, suggest that screening for M proteins and antibody levels in adults with invasive pneumococcal disease should be considered, according to the researchers, as the disease can reveal previously undiagnosed blood cancer and immunodeficiency.

“Currently, these tests are not routinely performed after a severe pneumococcal infection. As a result, we may miss patients with undiagnosed blood cancer or immunodeficiency and therefore missing the opportunity to initiate treatment,” says Tor Härnqvist, a doctoral student at the University of Gothenburg, an infectious disease physician at NU Hospital Group, and one of the lead authors.

Importance of tailoring vaccinations

Karin Bergman is a doctoral student in the same research group and an infectious disease physician at Södra Älvsborg Hospital. The study is part of her doctoral thesis, which she will soon defend at the University of Gothenburg, in which she also demonstrates how the pneumococcal bacteria causing severe disease have changed since the pneumococcal vaccine was introduced into the Swedish childhood vaccination programme.

The bacterial serotypes covered by the childhood vaccine have decreased sharply but have largely been replaced by other serotypes against which the vaccine offers no protection. Older adults and individuals with underlying conditions, particularly cancer and compromised immune systems, are frequently affected by these serotypes.

“The results show that recommendations on pneumococcal vaccines for adults need to take into account which vaccines are used in children and which bacterial serotypes subsequently circulate in the community,” says Karin Bergman.

Study: Invasive pneumococcal disease unmasks monoclonal immunoglobulins and antibody deficiencies: a multicenter prospective study in adults

Thesis: Invasive Pneumococcal Disease Bacterial, Viral, and Host Determinants of Susceptibility

Source: University of Gothenburg

One in Eight Cancers are Likely Caused by an Infection Worldwide – New Study

Photo by CDC on Unsplash

John (Eddie) La Marca, WEHI (Walter and Eliza Hall Institute of Medical Research) and Sarah Diepstraten, WEHI (Walter and Eliza Hall Institute of Medical Research)

Around 12% of the world’s total cancer cases in 2024 were likely caused by an infection, according to new research from the World Health Organization (WHO).

The study, published today in The Lancet Oncology, analysed the frequency and causes of different cancers, specifically examining the role of infections.

It linked 2.3 million new cancer cases to an infection. Most were caused by just five pathogens: Helicobacter pylori (4%), human papillomavirus, or HPV (4%), hepatitis B (2%), Epstein-Barr virus (1%) and hepatitis C (under 1%). These infections can cause more than 20 different types of cancer, including stomach, liver, blood and cervical cancers.

So, how can an infection cause cancer? And does this mean these cancers are preventable?

Did we already know about this link?

Some of the study authors have been researching this field for around thirty years. Their previous work investigated cancer cases caused by infections in 1990, 2002, 2008, 2012, and 2018. The proportion of cancer cases caused by infections may appear to have dropped during those years (from a high of 18% in 2002), but the authors stress these comparisons cannot really be made confidently, as the sources and quality of the data have changed over time.

In fact, the latest study wasn’t trying to compare between the years. Instead, it aims to highlight where controlling and preventing infections can help to reduce cancer rates.To make sense of this, it helps to know how infection is linked to cancer. Extensive research has dissected the molecular mechanisms behind this link, and we now know there are various ways infections can cause cancer.

How can a virus cause cancer?

A virus can (directly or indirectly) change the genes of the cell it infects (the host cell), making that cell more likely to grow out of control and eventually become a cancer.There are three main ways viruses can do this.

The first is by turning off the ability of a cell to destroy itself (for example, by inactivating the TP53 protein) or to stop dividing (for example, by inactivating the RB protein). A healthy cell would normally try to do these things if infected by a virus. The second way a virus can cause cancer is by inserting its own DNA into the host cell’s DNA, which can accidentally disrupt genes that control cell death or division (like those above). The third way is when the virus itself carries a gene that causes cancer (an oncogene). In many cases, the virus has picked up these by accident from another organism. The link between viruses and cancer is actually foundational to modern cancer science, and has helped scientists uncover the direct link between genetics and cancer we now take for granted.

What about bacteria and parasites?

It’s not just viruses that cause cancer. Infections from bacteria or parasites – such as Helicobacter pylori (best known for causing stomach ulcers), or Opisthorchis viverrini (a liver fluke, a type of parasitic worm) – can also lead to cancer. However, these work more indirectly than viruses. Long-term (chronic) infection by these types of organisms can cause significant stress to different tissues. Inflammation, normally a part of the body’s immune response, can then become overactive, damaging the tissues further. These stresses can result in cancer-causing DNA damage in cells, or lead to mistakes during cell division as the body tries to rapidly produce new cells to repair tissue damage. In both cases, the cells acquire genetic mutations that put them on the road towards becoming cancer.

Many cancers are preventable

Of course, there may be other mechanisms linking infections and cancer that we don’t know about but, overall, the connection between infections and cancer is indisputable. Critically, what this tells us – and what this new study into the rates of cancers caused by infections reinforces – is that many cancers are preventable.

In Australia, one of the best examples of preventing cancers caused by infections is the human papillomavirus (HPV) vaccine. This vaccine protects against certain strains of HPV strongly associated with cervical cancer, and is available to adolescents in Australia. Since the program began in 2007, HPV infections dropped by 90% among people eligible to receive the vaccine. Because of its success, Australia could be on track to eliminate cervical cancer by 2035. However, vaccination rates among 15-year-olds have fallen from 85.7% in 2020 to 79.5% in 2024, which is concerning. As is the case for all vaccines, a high proportion of the population need to be vaccinated to also protect those who, for health reasons, cannot be vaccinated. For HPV, the WHO and Australian target is to vaccinate 90% of 15-year-old girls by 2030.

Sadly, the new study also highlights that around 75% of cancers caused by infections were found in low- and middle-income countries.Treating infections that can lead to cancer – such as HIV, H. pylori, and hepatitis B and C – is one way to reduce cancer rates. Preventative measures also play a major role, including vaccinations, condoms and disease screening. However, the availability of these programs in poorer countries can be limited, and so access continues to be a major equity issue in combating cancer.

The authors would like to acknowledge the contribution of Amali Cooray from the Olivia Newton-John Cancer Research Institute to this article.

John (Eddie) La Marca, Senior Research Officer, Blood Cells and Blood Cancer, WEHI (Walter and Eliza Hall Institute of Medical Research) and Sarah Diepstraten, Senior Research Officer, Blood Cells and Blood Cancer Division, WEHI (Walter and Eliza Hall Institute of Medical Research) This article is republished from The Conversation under a Creative Commons license. Read the original article.

Blood Test Trends may Help Identify Patients at Increased Risk of Cancer

Among patients with unexplained weight loss, changes over time in routine blood test results were associated with overall and site-specific cancer diagnoses

Photo: Pixabay

Blood test trends alongside unexplained weight loss can improve triage for cancer testing, according to a study by Brian Nicholson and colleagues from the University of Oxford, UK, published September 17th in the open access journal PLOS Medicine.

Abnormal blood test results, such as low haemoglobin or increased platelet counts, can provide clues about a patient’s risk of developing cancer. However, monitoring trends over repeat tests could provide further clues in some instances, by identifying cancer-related changes in blood test results that do not appear abnormal. Assessing patterns in blood test abnormalities and trends alongside unexplained weight loss could enhance cancer risk assessment and support earlier diagnosis.

In this study, researchers examined trends in blood test results among patients with unexplained weight loss, a common non-specific symptom associated with multiple cancer types. The goal was to determine whether trends in 26 commonly used blood tests in primary care could improve cancer risk stratification compared to abnormalities on single blood tests.

Among the more than 275 000 patients included in the study, nearly 14 000 were subsequently diagnosed with cancer within six months, allowing researchers to relate abnormalities on single tests and trends over repeat blood tests to cancer diagnosis. Overall, 23 blood test trends were associated with overall cancer risk. Several abnormalities were also associated with specific cancer types. After accounting for age and sex, several blood test trends were more discriminative for cancer diagnosis than individual abnormal test results. For example, trends in white blood count and neutrophils were linked to lung cancer while trends in red blood cell count, haematocrit, and platelet-to-lymphocyte ratio were associated with prostate cancer.

The findings suggest that monitoring changes in routine blood test results in patients with unexplained weight loss could identify patients in primary care who would benefit from additional cancer testing.

Author Brian Nicholson adds, “We show how blood test results are made more accurate for cancer by adding patient age and sex. This relatively simple calculation could easily be performed at the laboratory.”

Author Pradeep Virdee states, “In some instances, monitoring how a patient’s blood test results change over time could offer further value. We plan to assess how well blood test abnormalities and trends inform cancer risk in patients with other types of non-specific symptoms, such as fatigue and vomiting.”

Provided by PLOS

Sunflower Month’s Hope that Lasts: The Baby who Inspired a Donor

Photo by William Fortunato on Pexels

A chance encounter in a hospital waiting area led to a remarkable full-circle moment when a South African stem cell donor unknowingly saved the life of the very child who inspired her to join the registry.

In October 2022, Petro was walking into a hospital in Centurion for a routine check-up when she stopped to speak to a grandmother sitting near the entrance with a baby on her lap. The little girl, just a few months old, was receiving treatment for leukaemia. Petro went in for her appointment, went home, and could not stop thinking about her.

“That was quite a powerful meeting, realising that this was a really sick baby, and that her life depended on having a life-saving stem cell transplant,” she recalls. Within days, she had ordered a swab kit and joined the South African stem cell registry.

The little girl was Lydia.

Her family had first noticed something was wrong after noticing a yellow cast on her skin in a photograph taken with her older brother, something that nobody had registered in the day-to-day. At four months old, Lydia was diagnosed with Infant Acute Lymphoblastic Leukaemia and admitted to hospital the same day. Long blocks of chemotherapy followed, along with recurring infections her weakened immune system could no longer fight, and a week in intensive care with pneumonia.

“When Lydia was diagnosed, our whole world changed,” her mother, Estelle, remembers.

Her medical team had been clear from the start that a stem cell transplant offered the best chance of survival. Towards the end of 2022, the family received the news they had been hoping for: a donor match had been identified. Shortly before the scheduled transplant, the planned donation was unable to proceed.

“This broke my heart,” Estelle shares. “It felt like we were back at the beginning again, and that was painful.”

The search resumed with no guarantee it would end differently. Only 30% of patients needing a transplant find a compatible donor within their own family. For Lydia, that meant her chances depended on an unrelated donor somewhere in the world whose tissue type matched hers.

When the call came, Petro was nearing 50 and half expected to be told she no longer qualified. “I was actually quite happy and honoured, because I knew this is it,” she explains. “I knew there was a patient on the other side who really needed this as a life-saving measure.”

She describes the donation process as straightforward. “It was nothing more than a blood donation times two, basically. It’s a few hours out of your day.” 

Lydia was admitted for her transplant in February and spent nearly seven weeks in isolation with her mother. Gradually, signs of recovery emerged. She began eating again. She started to put on weight.

Months later, once the confidentiality period had lapsed, Petro joined a WhatsApp call with Lydia’s family. She began telling them why she had registered: the hospital in Centurion, the baby, and the grandmother at the entrance. As she spoke, she noticed the family starting to smile. The grandmother was on the call too.

“Lydia’s mother told me that they were that patient, they were that family,” she says. “I was absolutely flabbergasted. What are the odds of that happening?”

Her own family took it just as hard. “My mother cries every time we talk about Lydia,” Petro adds. “She remembers seeing her at the hospital when she was so tiny.”

Lydia is now four years old. She has caught up on developmental milestones she had missed and has not been readmitted since the transplant. “She will always have a special place in my heart,” Petro says. “She’s got her whole life in front of her.”

The cost behind every match 

None of it happens without a swab kit, and a swab kit is not free. Signing up costs the person registering nothing, but every entry carries a cost, most of it in the laboratory tissue typing that turns two cheek swabs into a searchable set of markers. This year, Sunflower Month is being marked under the theme Hope That Lasts, with every financial contribution helping to fund another registration through the laboratory and onto the registry, where a searching medical team can find it.

Held each September, the initiative dates back to 1999 and the founding of The Sunflower Fund, after two young South Africans, Darren Serebro and Chris Corlett, were diagnosed with leukaemia. Corlett painted a picture during treatment and called it Sunflowers of Hope. Following their passing, a vision to grow the registry so patients would have a better chance of finding a match. More than two decades later, Lydia became one of those patients, diagnosed with the same illness.

South Africans between the ages of 17 and 55 who are in good health can register as stem cell donors at no cost.

Petro has one message for anyone weighing it up. “Take that responsibility seriously and really commit. You can mean the difference between life and death for a patient.”

Palesa Mokomele, Head of Community Engagement and Communications at DKMS Africa, says the gap between a willing volunteer and a usable match is a financial one. “Every contribution puts another swab through the laboratory and another name on the registry. If you are eligible, order a kit. If you are not, fund one. And say something about it to the people you know, because Petro only registered because a stranger at a hospital told her what was happening. This year’s theme is a reminder that something you do today can make a difference years from now, perhaps for someone you have never even met.”

Can Vitamin C Improve Outcomes in People with Pre-cancer Blood Disorders?

Phase 2 trial results warrant further study in a phase 3 trial.

Photo by Diana Polekhina on Unsplash

Vitamin C boosts the activity of cellular proteins called TET enzymes that help control which genes are turned on or off. Because decreased function of TET enzymes is a common driver of certain forms of blood cancer, researchers tested the effects of vitamin C supplements in patients at risk of developing such malignancies. Results of the investigators’ phase 2 clinical trial are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.

The randomised, double-blind, placebo-controlled EVITA trial enrolled 109 patients in Denmark and the United States who had either a blood condition that can turn cancerous or a low-risk form of blood cancer. At the start of the trial, 55 patients were randomly assigned to receive oral vitamin C (1000mg/day) and 54 were assigned to receive placebo, for a total of 12 months.

Although the primary endpoint (growth rate of precancerous or cancerous cells) was similar between groups, participants who received vitamin C experienced changes in inflammatory signaling that aligns with better outcomes. Also, anaemia, pneumonia, acute aseptic arthritis, and internal bleeding were less frequent (although gastrointestinal problems were more frequent) in patients taking vitamin C compared with those taking placebo.

At a median follow-up of 33.6 months (nearly 3 years) in the intention-to-treat population, 35 deaths were recorded, including 24 in the placebo group and 11 in the vitamin C group. An exploratory analysis of these data found that participants in the vitamin C group were more likely to survive during follow-up than those in the placebo group. This finding requires confirmation in a larger phase 3 clinical trial.

“The EVITA trial gives us a strong rationale to continue exploring if and how vitamin C might benefit people with certain pre-cancer or early-stage blood cancers. More work is needed but we are cautiously optimistic that these findings could inform future strategies to intercept leukemia development,” said co–senior author Peter A. Jones, PhD, DSc (hon), of Van Andel Institute, in Grand Rapids, Michigan. Jones is co-leader of the Van Andel Institute–Stand Up To Cancer (VAI–SU2C) Epigenetics Dream Team, which led the EVITA trial.

“We are encouraged by our findings and what they ultimately could mean for people with these early-stage blood disorders. Although it is too soon to make recommendations based on our results, we are hopeful that a larger study will give us more definitive answers,” added co–senior author Kirsten Grønbæk, MD, PhD, of Rigshospitalet, Copenhagen University Hospital in Denmark. Grønbæk is a longtime member of the VAI–SU2C Epigenetics Dream Team.

Source: Wiley

Air Crew Have Greater Risk of Radiation-related Cancer Death

Findings support efforts to protect US aircrews from cosmic radiation exposure

Photo by Daniel Eledut on Unsplash

Of more than 500 occupations in the United States, flight attendants and pilots have the highest and second-highest proportion of radiation-related cancer deaths, a new study has found.

The results support considering occupational radiation protections for U.S. aircrew members commensurate with their level of exposure, said senior author Anupam Jena, the Joseph P. Newhouse Professor of Health Care Policy in the Blavatnik Institute at Harvard Medical School, and team.

It’s been known that aircrew members receive the largest annual effective dose of ionising radiation of any workforce in the United States, largely due to exposure to cosmic radiation at high altitudes. Members of the profession are also more likely to be diagnosed with certain cancers than the general population. But studies have been limited as to whether this translates to higher rates of cancer mortality.

The new research, published August 17 in JAMA Internal Medicine, studied this question using a larger dataset and more statistical power than were previously available.

The study, led by first author Vishal Patel, HMS clinical fellow in surgery at Brigham and Women’s Hospital, used a single population-based data source – the National Vital Statistics System – rather than individual occupational or cancer cohorts. Patel and colleagues looked at all U.S. death certificates from 2020 to 2024. These records have only recently been linked to the occupation of the decedent. The records yielded data from nearly 13 million decedents across 503 occupations, including 14000 pilots and 7000 flight attendants.

The team applied what’s known as a common adjustment approach, which accounted for several factors other than occupation that may affect mortality. These included age at death, sex, race, ethnicity, educational attainment, and marital status.

The researchers analysed radiation- and non-radiation-related cancers across occupations. They also compared flight crew members to ground-based aviation workers.

Radiation-related cancers analysed here included breast cancer, central nervous system cancers, multiple myeloma, leukaemia (except chronic lymphocytic leukaemia), lymphoma, thyroid cancer, prostate cancer, melanoma, and non-melanoma skin cancers. (The team excluded lung cancer to reduce potential confounding with smoking.)

The team found that pilots and flight attendants had statistically significantly higher rates of death from breast, central nervous system, and prostate cancers and melanoma. Pilots also had a higher rate of leukaemia deaths.

In all, about 6.9% of deaths among flight attendants and 6.7% of deaths among pilots were from radiation-related cancers, according to the analysis. These proportions were higher than for any of the other professions, including nuclear technologists, who are routinely exposed to radiation from non-cosmic sources yet placed 12th on the list, the authors said. Aircraft mechanics and assemblers did not have higher rates than other occupations.

Rates of non-radiation-related cancer deaths among aircrew members were similar to the general U.S. population.

Aircrew accrue an estimated 3 to 6 millisieverts per year of cosmic radiation (depending on flight paths), an order of magnitude above the estimated 0.4 millisieverts received annually by an average air traveller taking 10 cross-country round-trip flights per year, according to the CDC.

The Federal Aviation Administration formally recognises pilots and flight attendants as occupationally exposed to ionizing radiation, but unlike other radiation-exposed workers or aircrew in other countries, U.S. aircrew are not subject to federal dose limits or monitoring requirements.

Original written by Katie Brace

Source: Harvard Medical School

Magnetic Pulses can Reprogram Immune Cells to Fight Breast Cancer

An innovative approach for breast cancer treatment uses localised and non-invasive pulsed electromagnetic fields to reprogram immune cells, turning them from tumour helpers to cancer killers

NUS researchers Mr Viresh Krishnan Sukumar (left), Associate Professor Alfredo Franco-Obregón (centre), and Dr Alex Tai (right) showed that the application of brief, intermittent and low intensity magnetic pulses can reprogram immune cells to eradicate breast cancer.

Researchers at the National University of Singapore (NUS) have demonstrated an innovative approach for targeted breast cancer therapy using pulsed electromagnetic fields (PEMFs). The NUS team successfully reprogrammed tumour-associated macrophages (TAMs), a corrupted class of immune cells that typically promote cancer growth, into an active anti-tumour state that attacks and destroys cancer cells.

The study, led by Associate Professor Alfredo Franco-Obregón from the Department of Surgery at the NUS Yong Loo Lin School of Medicine and the NUS Institute for Health Innovation & Technology, was published in the journal Smart Medicine on 4 June 2026. This discovery builds on their previous work, where they showed that brief PEMF exposure enhances uptake of doxorubicin (DOX), a chemotherapy drug, by breast cancer cells.

PEMF therapy applies intermittent, low-intensity magnetic pulses to targeted regions of the body over a short period of time. Assoc Prof Franco-Obregón has previously explored the effect of PEMFs on muscle development and oncology. In their latest study, the NUS team demonstrated that even without chemotherapy, PEMFs completely eradicated tumours in 75 per cent of tested preclinical models after just four 30-minute sessions.

“Our study represents a major advancement in breast cancer treatment by demonstrating the potential of PEMFs as a stand-alone, drug-free therapy, offering a possible future where patients could avoid chemotherapy and its debilitating side effects,” said Assoc Prof Franco-Obregón.

Breast cancer cases are projected to rise by a third, from 2.3 million in 2023 to more than 3.5 million by 2050, while annual deaths may nearly double from 764 000 to nearly 1.4 million. Cancer treatment faces challenges such as tumour heterogeneity, drug resistance, and treatment-related toxicities. Approaches targeting TAMs also faced difficulties such as off-target effects. The growing burden underscores the urgent need for innovative therapies to improve patient outcomes and save lives.

From cancer’s friends to foes

Breast cancer occurs when cells in the breast mutate and grow uncontrollably, forming a solid tumour. These cancer cells recruit and hijack nearby immune cells, corrupting them to protect the tumour, accelerate tumour growth, and encourage the spread of cancer (metastasis). Prominent among these recruited immune cells are TAMs, which are abundant in nearly all solid tumours.

There are two primary types of macrophages, M1 and M2. M1 macrophages are pro-inflammatory – the “soldiers” that eliminate threats like bacteria and viruses. M2 macrophages are anti-inflammatory – the “medics” that orchestrate wound healing and tissue repair once threats are cleared. Cancer cells corrupt most TAMs into adopting the M2 “medic” state, suppressing immune attacks against the tumour while facilitating tumour growth and metastasis.

The key to this macrophage reprogramming lies in a protein called TRPC1 (Transient Receptor Potential Canonical 1), which regulates the M1 state. Crucially, TRPC1 also allows cells to sense and respond to magnetic fields. In their experiments, the NUS team confirmed that a brief 10-minute exposure to PEMFs activated TRPC1 channels on M2-like TAMs, setting off a signalling cascade that converted them to the M1 state – essentially turning TAMs from helpful “medics” to aggressive cancer-killing “soldiers”. These activated TAMs then selectively target cancer cells while sparing healthy tissue. Furthermore, the same magnetic signature disrupts cancer’s ability to hijack TAMs, altering the TAM-cancer communication loop in both directions.

“We have identified a molecular “switch”, the specific cell signalling pathway that allows us to reprogram TAMs. Once reprogrammed, these immune cells actively hunt and devour cancer cells, obliterating the tumour,” said Assoc Prof Franco-Obregón. “With the non-invasive and targeted nature of PEMF therapy, we hope to provide patients an effective and safe alternative treatment, with fewer undesirable side effects.”

The NUS team is optimistic that their PEMF therapy can be a potential complementary treatment for other cancers beyond breast cancer. The PEMF device has successfully completed Phase 1 clinical trials and will soon be embarking on Phase 2 efficacy trials.

Pulses of hope for cancer patients

Assoc Prof Franco-Obregón shared that the same PEMF device used in this study has just successfully completed Phase 1 clinical trials, demonstrating its safety in humans. The team is now seeking partners to conduct Phase 2 efficacy trials to evaluate how well the PEMF treatment works in patients and to further advance its development towards clinical use.

“Since we previously showed that PEMFs selectively increased the uptake of DOX in breast cancer cells, we will be evaluating if our PEMF immunotherapy can work synergistically with chemotherapy for better results,” added Assoc Prof Franco-Obregón. “As the immune cells we reprogram are commonly found in most solid tumours, we are optimistic that our PEMF therapy could potentially be a complementary treatment for other cancers beyond breast cancer.”

Source: National University of Singapore

Cancer Cells Release Antioxidants to Prevent Immune Cells from Destroying Them

Killer T cells surround a cancer cell. Credit: Alex Ritter, Jennifer Lippincott Schwartz and Gillian Griffiths, National Institutes of Health (CC BY 2.0).

Molecules called reactive oxygen species, which include so-called ‘free radicals’, have long been viewed as damaging byproducts of our body’s metabolism – a reason why antioxidant supplements have been considered as a potential way of reducing cancer risk.

We’ve found a new way by which cancers shut down the immune system. When we block this process, tumours that don’t respond to some immunotherapies start responding to treatmentRahul Roychoudhuri

Now, scientists have discovered that certain immune cells depend on these very molecules to activate and destroy cancer cells, and that tumours exploit this dependency by releasing natural antioxidants to shut down the immune attack.

The findings, published today in Science, could help improve the effectiveness of cancer immunotherapies. 

Our immune system keeps us healthy by hunting down and destroying harmful material, including invading bacteria and viruses, but also cancer cells. It does so by deploying a number of different types of immune cells, including specialised cells known as T cells. These T cells hunt down and destroy tumour cells, but T cells need small amounts of reactive oxygen species to activate and switch on their killing ability.

A team at the University of Cambridge, UK, and Oregon Health & Science University, USA, analysed the fluid surrounding cells within tumours grown in mice and found that cancers chemically ‘smother’ T cells, stopping their activation and preventing them from destroying cancer cells. Tumours do this by releasing large amounts of a protein that is a natural antioxidant, Peroxiredoxin 1 (PRDX1), which mops up reactive oxygen species and deprives T cells of the activating signals they need to perform cancer killing. 

Next, the team used CRISPR gene-editing technology to create mouse cancer cells that could no longer make the antioxidant protein. They found that removing the capacity for the cancer cells to produce the antioxidant promoted immune-cell activity and limited tumour growth.

Finally, the team looked for the same mechanism in people. They analysed published data on the proteins released by human cancer cell lines, examined gene activity across thousands of human tumours, and isolated the fluid surrounding tumours removed from patients. All three approaches pointed the same way: human cancers also release PRDX1 into their surroundings, where it can strip away the reactive oxygen species that T cells depend on.

Dr Xan Wesolowski from the Department of Pathology at the University of Cambridge, one of the lead authors, said: “We tend to think of reactive oxygen species purely as damaging byproducts of metabolism. But we are increasingly understanding they have important functions within cells, and T cells need them to activate. Our study develops this picture, revealing that tumours can exploit this very dependency to evade elimination.”

The treatment of cancer is increasingly moving towards leveraging the immune system to eradicate the disease. However, while immunotherapies can be incredibly effective, they are only effective in some patients. Removing the ability of cancer cells to produce PRDX1 enhanced the cancer’s response to immunotherapy.

Professor Rahul Roychoudhuri, also from Cambridge’s Department of Pathology, said: “We’ve found a new way by which cancers shut down the immune system. When we block this process, tumours that don’t respond to some immunotherapies start responding to treatment. That tells us this is a pathway worth targeting therapeutically, and there are several ways we might be able to achieve this.”

Dr Robert Eil from the School of Medicine at Oregon Health & Science University said: “Our study suggests a possible way to boost T cell immunotherapies. Rather than using antioxidants, it could be that prooxidants can kickstart the T cells into action against tumour cells.”

The findings also carry broader implications. Several large randomised clinical trials have found that antioxidant supplements fail to reduce cancer risk, and in some cases worsen outcomes. The discovery that T cells depend on reactive oxygen species to fight tumours may help to explain why: antioxidants could inadvertently blunt the immune system’s ability to attack cancer. However, the team stresses that as its findings are in preclinical laboratory models, and people living with cancer should not change their treatment or diet without medical advice.

The research was largely funded by the Medical Research Council, European Research Council, Wellcome and the National Institutes of Health/National Cancer Institute.

Reference

Wesolowski, AJ, et al. Tumor-derived antioxidants suppress immunity by depriving T cells of reactive oxygen species. Science; 3 Sept 2026; DOI: 10.1126/science.adz8203

Republished from University of Cambridge under a Creative Commons licence. Read the original article.