Insight
Study reveals how bacteria can promote breast cancer
Harmful bacteria may worsen breast cancer by switching on an enzyme that damages DNA and helps tumours grow, researchers say.
The study found that pathogenic bacteria seen in gut and breast tissue, including Bacteroides fragilis, Fusobacterium nucleatum and Escherichia coli, boosted activity of spermine oxidase (SMOX).
This rise was linked to DNA damage, tumour growth and metastasis (the spread of cancer) in lab and animal models.
The work, led by researchers at the Johns Hopkins Kimmel Cancer Center, links microbial dysbiosis (an imbalance of helpful and harmful bacteria) with tumour behaviour and points to SMOX as a possible treatment target.
“Microbes don’t just reside in our gut. They can directly influence cancer behaviour,” said Dipali Sharma, professor of oncology at the centre and the study’s lead investigator.
“We found that an overabundance of certain pathogenic bacteria triggers inflammation and activates SMOX, producing reactive oxygen species that damage DNA and fuel tumour growth.
“By blocking SMOX, we were able to dramatically reduce tumour formation in our preclinical models.”
The researchers focused on enterotoxigenic Bacteroides fragilis (ETBF), a strain that secretes a toxin that can reshape bacterial communities and has been linked to cancer.
When breast cancer cells or mouse mammary tissue were exposed to ETBF or its toxin, SMOX levels surged, driving oxidative stress (cell damage caused by reactive molecules), inflammation and genomic instability, where DNA becomes more prone to mutations.
Further experiments found that F. nucleatum and toxin-producing E. coli had similar effects, while non-pathogenic bacteria did not.
The bacteria also triggered rises in inflammatory cytokines such as interleukin-6 (IL6) and tumour necrosis factor-alpha (TNFα), which further increased SMOX expression and activity.
“Inflammatory cytokines stimulate SMOX, SMOX generates oxidative stress, and the resulting DNA damage helps tumours grow and spread,” said Deeptashree Nandi, a postdoctoral fellow working with Sharma and first author of the study.
“This establishes a self-perpetuating loop.”
To test whether the bacterial effect could be blocked, the investigators treated breast cancer cells in laboratory and animal models with two SMOX inhibitors (MDL72527 and SXG-1).
Both suppressed SMOX activity, reduced markers of DNA damage and halted tumour progression, even in the presence of pathogenic bacteria.
Mice colonised with ETBF developed more, faster-growing mammary tumours than uninfected controls, but those given SMOX inhibitors had smaller tumours, fewer metastases and lower markers of oxidative DNA damage.
“These findings suggest that pharmacological inhibition of SMOX could be a viable strategy to counteract the cancer-promoting effects of microbial dysbiosis,” Sharma said.
The team also found the mechanism was not limited to a single strain.
Pathogenic F. nucleatum, E. coli and Mycobacterium tuberculosis culture extracts also triggered SMOX activity and DNA injury in breast cancer cells.
“This convergence across distinct bacterial species suggests that SMOX may represent a shared molecular hub through which microbes influence cancer biology,” Sharma said.
The findings suggest that measuring SMOX activity or analysing microbial composition could help identify women at higher risk of aggressive disease.
The researchers are exploring SMOX inhibitors as potential additions to standard therapies and investigating how microbe-driven inflammation affects tumour immune responses.
“Understanding how bacteria communicate with cancer cells opens entirely new avenues for prevention and treatment,” said Sharma.
“If we can interrupt that conversation, particularly by targeting SMOX, we may be able to slow or even stop cancer progression in patients affected by microbial imbalance.”
An early PET scan after one cycle of chemotherapy may help predict how aggressive breast cancer responds to treatment, a study suggests.
Research led by The Institute of Cancer Research, London and King’s College London suggests that an early scan taken after one cycle of chemotherapy could help predict how well a patient’s cancer will respond to treatment.
The study focused on patients with triple-negative breast cancer (TNBC), an aggressive form of the disease in which cancer cells lack receptors for the hormones oestrogen and progesterone, as well as the HER2 protein.
Patients with TNBC are usually treated with chemotherapy prior to surgery. While many respond well, residual disease at surgery, typically around six months later, is associated with a significantly poorer prognosis. Identifying people sooner who are unlikely to respond remains a major clinical challenge.
The research explored whether using PET imaging shortly after treatment begins, rather than relying only on MRI scans later in the treatment process, could provide earlier insight into how a patient’s cancer is responding. Twenty-two patients were recruited, with fourteen undergoing FDG-PET scans before treatment and after the first cycle of chemotherapy.
The findings, published in Clinical Cancer Research, showed that changes seen on PET scans after just one cycle of chemotherapy were strongly associated with subsequent response, including whether there was no detectable cancer, known as a complete response, by the end of treatment. Importantly, early PET response showed stronger associations with treatment outcomes than standard mid-treatment MRI scans in this study.
Being able to identify patients who are not responding well at an early stage could allow clinicians to adjust treatment sooner or consider alternative approaches. These findings may also support future strategies to better tailor treatment intensity to individual patients.
The study also compared two types of PET tracers, FDG and FLT, to determine which was most suitable. While both met the study’s technical criteria, FDG-PET was selected for further evaluation due to its better image quality, greater consistency and wider use in clinical practice.
The research also explored how imaging changes after just one cycle of chemotherapy relate to the body’s immune response to treatment. Biopsies taken before and after the first cycle of chemotherapy showed that an increase in immune cells within the tumour was strongly associated with both early PET changes and improved treatment outcomes.
The researchers emphasise that these findings now need to be validated in larger studies. Future work will aim to confirm these results in broader patient groups and explore more accessible imaging approaches, such as ultrasound, alongside PET and MRI.
Sheeba Irshad, professor of cancer immunology at King’s College London and lead of the Breast Cancer Now KCL Research Unit, said:
“In patients who had PET scans both before treatment and after the first cycle, we found that this early scan could predict whether they were likely to achieve a complete response by the end of treatment. These findings highlight the potential of early imaging to guide treatment decisions, and now need to be validated in larger, modern clinical trials.”
Andrew Tutt, professor of breast oncology at The Institute of Cancer Research, London, said:
“Research that helps us determine early who is already benefitting from standard neoadjuvant chemotherapy and who might benefit from clinical trials to find better treatments is vital. This study shows that FDG-PET may have great value in this regard. We hope to be able to design studies that further investigate and validate these findings.”
The study was supported by funding from King’s College London and Guy’s and St Thomas’ NHS Foundation Trust, Breast Cancer Now, Cancer Research UK, and Guy’s and St Thomas’ Charity.
Ki-67, a protein used to measure tumour growth, may also help prevent chromosome errors that drive cancer, a study suggests.
The findings could change how scientists view Ki-67, a marker commonly used in breast cancer and other tumours to assess how quickly cancer cells are growing.
Researchers found the protein may help preserve genome stability by maintaining the structural integrity of centromeres, key parts of chromosomes that help ensure DNA is shared correctly during cell division.
The research was led by professor Paola Vagnarelli at Brunel University of London in collaboration with scientists at the University of Edinburgh and the Technical University of Berlin.
Professor Vagnarelli said: “Doctors already measure Ki-67 to see how aggressive a cancer might be. But our results suggest it is actually helping maintain genome stability.
“That means it may be more than a marker. It could potentially also be a therapeutic target.”
The study examined three proteins that attach to chromosomes during cell division and help rebuild the molecular system that tells each new cell what kind of cell it is.
Every human cell carries identical DNA. What makes a liver cell different from a brain cell is which genes are switched on and which are kept inactive.
When a cell divides, that entire system of switches must be rebuilt. The three proteins involved in this process were Ki-67, Repo-Man and PNUTS.
Vagnarelli’s team developed a method that individually removes each protein from a living cell at the precise point of division. Older techniques could not isolate that moment cleanly.
They found that cells rely on all three proteins to reset themselves after division, but each failed in a different way when removed.
Without PNUTS, gene activity spiralled out of control and thousands of genes switched on at once.
Without Repo-Man, cells escaped safety checkpoints that usually stop damaged or abnormal cells from continuing to divide.
“What we didn’t expect was how clean the separation was,” said Vagnarelli.
Each protein fails in its own specific way. There is no redundancy, no safety net. Which means there are three separate points at which this process can go wrong.
“When the system breaks down, cells can emerge with the wrong number of chromosomes. That condition, called aneuploidy, is seen in disorders such as Down syndrome and in many cancers.
“We also found that these chromosome errors can trigger inflammatory signals inside the cell.”
Aneuploidy means a cell has too many or too few chromosomes, which can disrupt normal growth and function.
Inflammatory signals are chemical messages that can make a cell behave as if it is responding to injury or infection.
“These cells behave almost as if they are under attack,” said Vagnarelli.
“The immune response switches on because the genome is unstable.
“That link between chromosome imbalance and inflammation could help explain patterns we see in several diseases.”
The researchers said the findings may help cancer scientists better understand how chromosome instability, loss of gene regulation and cells dividing before they are ready contribute to tumour growth.
They said understanding the normal machinery that prevents these errors may help researchers find ways to push cancer cells into making mistakes they cannot survive.
“We now have a clearer map of the machinery that resets the cell after division,” said Vagnarelli.
“That knowledge gives us a starting point for thinking about new therapeutic approaches.”
After more than a decade of campaigning, doctors around the world have agreed to rename polycystic ovary syndrome (PCOS).
It is hoped the new name, polyendocrine metabolic ovarian syndrome, or PMOS, will help end the misconception that the condition is all about cysts, which campaigners say has contributed to missed diagnoses and inadequate treatment.
The condition affects one in eight women, or 3.1m women and girls in the UK, and is linked to hormone fluctuations that can affect weight, mental health, skin and the reproductive system.
The renaming was spearheaded by UK patient charity Verity alongside Professor Helena Teede, director of Melbourne’s Monash Centre for Health Research and Implementation.
It followed 14 years of consultation with clinicians and patients around the world.
The new name was published in a consensus statement on May 12 and announced at the European Congress of Endocrinology in Prague.
The paper states that PCOS should now be referred to as PMOS.
“This is a landmark moment that will lead to desperately-needed worldwide advancements in clinical practice and research,” said Professor Teede.
“It was heart-breaking to see the delayed diagnosis, limited awareness and inadequate care afforded those affected by this neglected condition.”
When doctors first named PCOS in 1935, they thought it was mainly caused by physical changes to the ovaries.
Decades of research have since changed that understanding, with clinicians now agreeing the condition is far more complex.
“What we now know is that there is actually no increase in abnormal cysts on the ovary and the diverse features of the condition were often unappreciated,” Professor Teede added.
“A name change was the next critical step towards recognition and improvement in the long term impacts of this condition.”
The exact cause of the condition is still unknown, though it is thought to be linked to abnormal hormone levels and is associated with insulin resistance and raised levels of testosterone and luteinising hormone.
Insulin resistance means the body does not respond properly to insulin, the hormone that helps control blood sugar. Luteinising hormone helps regulate ovulation.
Common symptoms listed by the NHS include irregular periods or no periods at all, difficulty getting pregnant, excessive hair growth, weight gain, thinning hair, oily skin and acne.
Campaigners have acknowledged that the name change could cause temporary confusion.
“Despite decades of tireless advocacy to improve awareness, we recognised that the risk of change would be worth the reward,” said Rachel Morman, chairwoman of Verity.
“This shift will reframe the conversation and demand that it is taken as seriously as the long-term, complex health condition it is.”
It is also unclear if, or when, the NHS will change the language it uses.
An NHS England spokesperson said: “We routinely review and update content on the NHS website to ensure it reflects the latest clinical advice and will carefully consider these recommendations.
“The NHS will also continue our work to improve women’s healthcare, including for this important group, which involves giving women more choice over their care, bringing down waiting times, and delivering more care in communities.”
News4 weeks agoWomen’s digital health market set to reach US$5.28 billion in 2026 – report
Fertility4 weeks agoWhy the UK’s fertility rate keeps falling – and what it means if you’re trying now
Wellness4 weeks agoWomen’s HealthX unveils Northwell Health, Corewell Health, Biogen & more to headline Chronic Disease stage
Opinion3 weeks agoWhat Maternal Mental Health Month reveals about where postpartum support actually breaks down
Fertility4 weeks agoToxins and climate harms having ‘alarming’ effect on fertility, research warns
Insight3 weeks agoNIH Grant terminations disproportionately impact minority scientists, research finds
Adolescent health2 weeks agoWUKA brings Period-Positive Pool Party to London Aquatics Centre to keep girls swimming through puberty
Fertility4 weeks agoResearcher explores weight loss jab impact on PCOS
1 Comment