Magnetic pulses promote uptake of chemotherapy drug

The advance from researchers at the National University of Singapore could lead to precision-driven cancer therapies with fewer side effects. Their findings are detailed in the journal Cancers. 

The study, led by Associate Professor Alfredo Franco-Obregón, principal investigator at the Institute for Health Innovation & Technology (iHealthtech) at NUS and faculty member of the Department of Surgery at NUS Yong Loo Lin School of Medicine (NUS Medicine), 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.

DOX 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 that can damage healthy tissues, leading to side effects ranging from mild to severe, including cardiomyopathy and muscle atrophy.

To address these challenges, the NUS 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 called 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.

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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.

“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, the paper’s first author and a PhD candidate at NUS Centre for Cancer Research (N2CR).

According to the World Health Organisation, 2.3 million women were diagnosed with breast cancer in 2022.

“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 Assistant Professor Joline Lim, principal investigator at N2CR and senior consultant, Department of Haematology-Oncology, National University Cancer Institute, Singapore. “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.”

According to NUS, future work will focus on translating the team’s findings into clinical practice by localising magnetic field exposure specifically to tumours in patients.

“Our approach will be patented and form the foundation for a startup specialising in breast cancer treatment. We are currently in discussions with potential investors in Southeast Asia and the United States to translate this technology from bench to bedside,” said Assoc Prof Franco-Obregón.