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Researchers at the National University of Singapore (NUS) have introduced an innovative non-invasive technique aimed at enhancing the effectiveness of chemotherapy while minimizing its adverse side effects.
Through the application of short, localized magnetic field pulses, the research team has demonstrated a marked increase in the absorption of doxorubicin (DOX)—a widely utilized chemotherapy medication—into breast cancer cells, with minimal effect on surrounding healthy tissues. This targeted approach potentially leads to better outcomes in cancer treatment and lessens the negative impacts typically associated with chemotherapy.
The study, spearheaded by Associate Professor Alfredo Franco-Obregón, who serves as Principal Investigator at the Institute for Health Innovation & Technology (iHealthtech) at NUS, marks a significant advancement in the field. It is the first systematic investigation to reveal how pulsed magnetic fields can boost the uptake of DOX in cancer cells, subsequently allowing for effective tumor suppression even at lower dosages of the drug.
This groundbreaking research was published in the journal Cancers on November 18, 2024, and builds upon earlier research from 2022 that identified certain cancer cells’ heightened sensitivity to magnetic field therapy.
Targeted therapy for enhanced chemotherapy efficacy
DOX is frequently employed in the treatment of breast cancer, functioning by binding to DNA components and disrupting the processes of cell replication and respiration, ultimately leading to cancer cell death. Although effective, DOX is a non-selective agent, posing risks of harm to healthy tissues and causing side effects that can range from mild to severe, including cardiomyopathy and muscle wasting.
To address the challenges posed by conventional chemotherapy, the researchers at NUS devised a novel methodology involving brief magnetic field pulses to selectively enhance the absorption of DOX into breast cancer cells. Their findings highlighted the significance of a calcium ion channel called TRPC1, which is prevalent in aggressive cancers like breast cancer. The application of magnetic fields activates TRPC1, thereby improving the transport of DOX into the cancer cells.
In their experiments, the researchers compared the effects of magnetic field therapy on human breast cancer cells versus healthy muscle cells. The results indicated that the cancer cells absorbed significantly more DOX when subjected to magnetic pulses, while the healthy tissues experienced minimal targeting. A mere ten minutes of magnetic exposure was sufficient to halve the concentration of the drug necessary for comparable cancer cell lethality, particularly at lower DOX dosages.
Furthermore, healthy muscle cells demonstrated no increased rate of cell death with the combined application of DOX and magnetic pulses, indicating a protective effect for non-cancerous tissues. The research team confirmed that reducing TRPC1 expression or inhibiting its activity nullified these effects, confirming its vital role in the drug uptake process. “Notably, enhancing TRPC1 levels resulted in improved DOX absorption, suggesting it could serve as a promising therapeutic target for aggressive cancers,” stated Mr. Vinesh Krishnan Sukumar, the first author and a PhD candidate at the NUS Centre for Cancer Research.
“The promising aspect of this mechanism is its strongest efficacy at lower concentrations of the drug, which allows us to focus on cancer cells more effectively while alleviating the strain on healthy tissues,” Assoc Prof Franco-Obregón remarked.
As breast cancer continues to be the leading cause of cancer-related fatalities among women globally, there is an urgent need for innovative treatment strategies. “Many women undergoing chemotherapy experience side effects that can lead to dose reduction or, in severe cases, the premature termination of treatment,” explained Assistant Professor Joline Lim, a member of the research team and Senior Consultant at the National University Cancer Institute, Singapore. “Additionally, prolonged exposure to high doses may contribute to drug resistance, making this targeted approach a significant opportunity to enhance treatment outcomes while maintaining patients’ quality of life.”
Progress in precision oncology
The magnetic-assisted methodology developed by the team tackles one of chemotherapy’s most significant hurdles: its toxicity to healthy tissues. By specifically targeting drug uptake in cancer cells, this strategy has the potential to substantially mitigate the systemic side effects often faced by breast cancer patients. This improvement not only enhances treatment effectiveness and patient quality of life but may also encourage those who are hesitant about treatment to begin therapy earlier. The research further highlights the importance of biomarkers like elevated TRPC1 levels in advancing personalized treatment options in cancer care.
Future efforts will concentrate on transitioning these findings into clinical application by precisely localizing magnetic field exposure to tumors in patients. This step would further validate the possibility of reducing systemic doses of DOX while optimizing localized delivery directly to cancer cells.
“We intend to patent our approach, which will form the basis for a startup that focuses on breast cancer treatment. We are currently engaged in discussions with potential investors both in Southeast Asia and the United States to facilitate the transition of this technology from laboratory research to practical application,” concluded Assoc Prof Franco-Obregón.
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