Cancer
Chemotherapy in breast cancer treatment boosted with localised magnetic fields
Researchers have developed a non-invasive method to improve the effectiveness of chemotherapy while reducing its harmful side effects using localised magnetic fields.
By applying brief, localised pulses of magnetic fields, researchers have demonstrated a significant increase in the uptake of doxorubicin (DOX), a widely used chemotherapy drug, into breast cancer cells, with minimal impact on healthy tissues.
This selective uptake enables more precise targeting of cancer cells, potentially improving treatment outcomes and reducing the adverse effects often associated with chemotherapy.
The study is the first to systematically show how pulsed magnetic fields enhance DOX uptake in cancer cells. The team also showed that this approach could suppress tumours at lower drug doses.
The team’s research builds on earlier work from 2022, which first revealed that certain cancer cells are more vulnerable to magnetic field therapy.
DOX is a commonly used chemotherapy drug for breast cancer. It works by binding to DNA components and disrupting cell replication and respiration, which then kills off cancer cells.
Despite its efficacy, it is a non-selective drug, which means it can also damage healthy tissues, leading to side effects ranging from mild to severe, including cardiomyopathy and muscle atrophy.
To address these challenges, NUS Medicine researchers developed a novel approach that uses brief pulses of magnetic fields to selectively increase DOX uptake into breast cancer cells.
Their study revealed the role of a calcium ion channel known as TRPC1, which is often found in aggressive cancers, including breast cancer. Magnetic field exposure activates TRPC1, enhancing its ability to facilitate the entry of DOX into cancer cells.
The researchers conducted experiments comparing the effects of the magnetic field therapy on human breast cancer cells and healthy muscle cells. They found that breast cancer cells took in significantly more DOX when exposed to magnetic pulses, while normal tissues were not targeted as much.
A 10-minute magnetic field exposure reduced the drug concentration needed for similar amount of cancer killing by half, particularly at low doses of the drug.
In contrast, healthy muscle cells did not show an increase in cell death in response to the combination of DOX and magnetic pulses indicating greater protection for non-cancerous tissues.
The team also demonstrated that reducing TRPC1 expression or blocking its activity eliminated this effect, which confirms the crucial role of TRPC1 channels in the process.
“Importantly, when we increased the amount of TRPC1, we observed an increase in DOX uptake — this means that TRPC1 can be used as a viable therapeutic target for aggressive cancers,” said Vinesh Krishnan Sukumar, first author at NUS Centre for Cancer Research (N2CR) under NUS Yong Loo Lin School of Medicine.
“What’s promising is that this mechanism works strongest at low drug concentrations, enabling us to target cancer cells more effectively while reducing the burden of chemotherapy on healthy tissues,” professor Franco-Obregón said.
With breast cancer remaining the leading cause of cancer-related deaths among women worldwide, the need for novel treatment strategies is urgent.
“The majority of women who undergo chemotherapy experience side effects from treatment, and in some cases, doses of chemotherapy need to be reduced, or in severe cases, stopped prematurely,” said research team member professor Joline Lim.
“Moreover, prolonged exposure to high-dose chemotherapy can also lead to drug resistance. This targeted approach represents an excellent opportunity to potentially improve treatment outcomes while preserving patients’ quality of life.”
AI may help speed breast cancer diagnosis for high-risk women after abnormal mammograms, a study suggests.
Women with abnormal mammograms often wait weeks to learn whether they have breast cancer.
Researchers at UC San Francisco and UC Berkeley said an AI-guided workflow could help reduce that wait by quickly identifying those most likely to have the disease. Some women could move from imaging to evaluation, and sometimes biopsy, in a single day.
Dr Maggie Chung, first author of the study, said: “This is a really an exciting time.
“This moves us closer to personalised care, where we can tailor a plan so that each patient gets the right intervention at the right time.”
The study used an open-source AI model called Mirai.
The model was trained on hundreds of thousands of mammograms linked to patients’ cancer outcomes.
A mammogram is an X-ray scan of the breast used to look for signs of cancer. A biopsy involves taking a small tissue sample to test for disease.
The AI tool is designed to detect subtle patterns in screening mammograms and predict a woman’s cancer risk.
Researchers at UC San Francisco and UC Berkeley applied the model to more than 4,100 screening mammograms at Zuckerberg San Francisco General Hospital and Trauma Center.
Mirai identified 525 women, about 12.7 per cent of screened patients, as high risk.
Those patients could receive an interpretation of their mammograms immediately after the scan and have additional diagnostic imaging for suspicious areas on the same day.
Some women who needed biopsies were also able to have them on the same day.
The researchers said Mirai reduced the wait time for diagnostic evaluation from several weeks to about an hour.
For women who were ultimately diagnosed with breast cancer, it reduced the average wait for biopsy from more than two months to fewer than 10 days.
The researchers stressed that Mirai does not replace radiologists or make diagnoses on its own.
Instead, it acts as a triage tool to help physicians identify the patients who can benefit most from accelerated care.
The team analysed more than 114,000 archival mammograms before launching the programme, to ensure the model would capture enough high-risk patients without overloading the clinic with too many expedited evaluations.
The researchers said they hope AI will support a more personalised approach to breast cancer screening tailored to each patient’s breast cancer risk.
Chung said: “Right now, many women follow the same screening schedule but their individual risk can be very different.
“AI risk assessment gives us the chance to identify the women most likely to benefit from expedited care and get them what they need.”
Adam Yala, senior author of the study and a data scientist at UC Berkeley, said: “This is a powerful example of how AI can be a collaborative partner for physicians.
“It shows how we can improve care when we bring clinicians and data scientists together to design these systems.”
A genomic test may help some women with breast cancer avoid chemotherapy, with near-identical outcomes in an international trial.
The findings suggest patients with a low test score could be treated with hormone therapy alone without increasing the risk of their cancer returning.
Researchers said the results could support more personalised treatment decisions and spare some women the side-effects of chemotherapy.
Prof Rob Stein, the trial’s chief investigator and a professor of breast oncology at UCL, said: “Optima addresses a longstanding challenge in breast cancer care: identifying who truly benefits from chemotherapy and who does not.
“Our findings show that many patients can safely avoid chemotherapy without compromising their outcomes.
“These results mark an important and significant step toward more personalised treatment.
“The trial has successfully used tumour biology to guide decisions rather than relying solely on traditional clinical features.”
Breast cancer treatment usually involves surgery to remove tumours. Chemotherapy is then often recommended if doctors believe there is a risk the disease will return.
Chemotherapy can cause side-effects including hair loss, rashes, nausea, insomnia and fatigue. Some women may also face longer-term consequences such as infertility, cognitive impairment or early menopause.
The Optima trial followed more than 4,000 patients with newly diagnosed breast cancer in the UK, Norway, Sweden, Australia, New Zealand and Thailand.
The trial was led by University College London.
One woman who took part in the trial told the Guardian that being able to skip chemotherapy felt “like Christmas”. Nine years after being diagnosed, taking the test and skipping chemotherapy, she is healthy and enjoying a full and active life.
The trial tested whether a genomic test could identify which patients need chemotherapy and which could safely avoid it.
The Prosigna test, made by diagnostics company Veracyte, analyses the activity of 50 genes in tumour tissue. It identifies the molecular subtype of the cancer and gives a score estimating the risk of breast cancer returning in the next 10 years.
The randomised trial involved 4,429 patients aged 40 or over with hormone-positive breast cancer. Hormone-positive breast cancer grows in response to hormones such as oestrogen or progesterone. It is the most common form of breast cancer, accounting for up to 80 per cent of cases globally.
Participants were assigned to one of two groups. In the standard treatment group, patients received chemotherapy followed by hormone therapy.
In the second group, patients had their tumours analysed using the genomic test. Those with a high score received chemotherapy and hormone therapy. Those with a low score received hormone therapy alone.
Radiotherapy and other treatments were given as usual in both groups.
In the second group, outcomes were very similar whether chemotherapy was given or not. Five years after treatment, 95 per cent of patients who had chemotherapy and hormone therapy were alive and free from breast cancer recurrence, while 94 per cent of those who skipped chemotherapy were also alive and recurrence-free.
The findings suggest chemotherapy offered little or no additional benefit for patients with low test scores.
Some men also took part in the study, but researchers said there were too few to draw firm conclusions for this group.
The trial received funding from the National Institute for Health and Care Research, Veracyte and cancer charities.
Prof Iain MacPherson, a co-chief investigator and professor of breast oncology at the University of Glasgow, said: “Optima provides robust, practice-changing evidence that we can safely reduce the use of chemotherapy for many patients with hormone-sensitive breast cancer.
“These findings represent a major step forward in delivering more personalised, precise care, ensuring that treatment decisions are driven by what will genuinely improve outcomes for patients, while avoiding unnecessary toxicity.
“The potential impact for both patients and health services is substantial.”
The FDA has delayed approval of camizestrant while it reviews new analyses submitted by AstraZeneca after advisers voted against the breast cancer drug.
The US regulator had been considering whether to approve the oral treatment after a phase 3 switching study in a specific group of breast cancer patients.
Camizestrant is an oral SERD, or selective oestrogen receptor degrader. These drugs are designed to block and break down oestrogen receptors that can help some breast cancers grow.
AstraZeneca filed for approval based on the phase 3 Serena-6 trial, which tested a treatment-switching approach.
Patients in the study received an aromatase inhibitor and a CDK4/6 inhibitor. Aromatase inhibitors lower oestrogen levels, while CDK4/6 inhibitors are targeted cancer drugs that help slow cancer cell growth.
After detecting an ESR1 mutation, investigators switched the aromatase inhibitor to camizestrant.
An ESR1 mutation is a change in a gene linked to the oestrogen receptor. It can make some breast cancers less responsive to standard hormone treatments.
AstraZeneca said switching to camizestrant was linked to a 56 per cent increase in progression-free survival.
Progression-free survival measures how long a patient lives without their disease getting worse.
However, the FDA raised questions about the study design.
An FDA advisory committee later voted six to three that AstraZeneca had failed to show camizestrant provides a clinically meaningful benefit.
The vote was a setback for the company’s hopes of approval, although the FDA can go against advisory committee recommendations.
After the setback, AstraZeneca submitted additional analyses requested by the FDA.
The company said the analyses include data on circulating tumour DNA clearance linked to longer-term efficacy outcomes.
Circulating tumour DNA refers to fragments of genetic material from cancer cells that can be found in the blood.
AstraZeneca is expected to share the data next week at the American Society of Clinical Oncology annual meeting.
The FDA has now delayed its ruling while it reviews the additional information. AstraZeneca did not provide a new decision date.
Three-month delays are typical and, during the second Trump administration, have been common.
After budget cuts reduced its workforce, the FDA delayed rulings on assets including Bayer’s Lynkuet, Biohaven’s troriluzole and Sanofi’s tolebrutinib. The FDA reportedly blamed a “heavy workload and limited resources” for one delay.
The agency has continued to delay rulings this year, with Biogen, Savara and Travere Therapeutics among the companies to say the FDA has extended reviews of their drugs.
Like AstraZeneca, those three companies faced delays after submitting additional information that the agency needed time to review.
If the additional analyses address the regulator’s concerns, AstraZeneca could still secure approval for a drug it has estimated could generate peak sales of more than US$5bn.
Guggenheim Securities analysts recently described the Serena-6 study as “a limited commercial opportunity in our and [AstraZeneca’s] view”.
AstraZeneca is also running two adjuvant studies and a trial in a first-line setting as it seeks to position camizestrant across different stages of breast cancer care.
Adjuvant treatment is given after primary treatment, such as surgery, to reduce the risk of cancer returning. First-line treatment is the first therapy given for a disease.
Roche reported the failure of its rival oral SERD in first-line breast cancer in March, but AstraZeneca executives have argued that their trial designs and drug candidate are different.
Last week, Europe’s Committee for Medicinal Products for Human Use issued a positive opinion on camizestrant.
The drug is expected to be marketed as Etcamah in Europe.
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