Researchers have created a method that is non-invasive and enhances the effectiveness of chemotherapy while minimizing its negative side effects. By using short, targeted magnetic field pulses, the team significantly boosted the absorption of doxorubicin (DOX), a common chemotherapy medication, into breast cancer cells, affecting healthy tissues only slightly.
Researchers at the National University of Singapore (NUS) have created a technique that is non-invasive and enhances the effectiveness of chemotherapy while minimizing its negative side effects.
By utilizing brief, targeted magnetic field pulses, the researchers showed a remarkable increase in the absorption of doxorubicin (DOX), a well-known chemotherapy agent, into breast cancer cells, with very little effect on healthy tissues. This precise absorption allows for better targeting of cancer cells, which may lead to improved treatment results and fewer adverse reactions typically linked with chemotherapy.
The study was led by Associate Professor Alfredo Franco-Obregón, a Principal Investigator at the Institute for Health Innovation & Technology (iHealthtech) at NUS and a faculty member in the Department of Surgery at the NUS Yong Loo Lin School of Medicine (NUS Medicine). This research is the first to systematically demonstrate how pulsed magnetic fields can enhance the uptake of DOX in cancer cells. The findings also suggest that this method could suppress tumors while using lower doses of the medication.
Published in the journal Cancers on November 18, 2024, this research builds on previous studies from 2022 that indicated certain cancer cells are particularly susceptible to magnetic field therapy.
Targeted therapy for improved chemotherapy results and reduced side effects
DOX is a frequently used chemotherapy agent for breast cancer. It operates by attaching to components of DNA, disrupting both cell replication and respiration, ultimately leading to the destruction of cancer cells. Despite its effectiveness, DOX is a non-selective medication, meaning it can also harm healthy tissues, leading to side effects that can vary from mild to severe, including heart problems and muscle wasting.
To tackle these issues, the NUS team devised an innovative method that employs short magnetic pulses to selectively enhance DOX absorption in breast cancer cells. Their research identified the relevance of a calcium ion channel named TRPC1, which is often present in aggressive types of cancer, including breast cancer. Exposure to magnetic fields activates TRPC1, thereby improving its ability to allow DOX to enter cancer cells.
In their experiments, the researchers compared the effects of magnetic field therapy on human breast cancer cells against healthy muscle cells. They discovered that breast cancer cells absorbed substantially more DOX when subjected to magnetic pulses, whereas normal tissues were not as significantly impacted. Just 10 minutes of exposure to the magnetic field halved the concentration of the drug required to achieve similar cancer cell destruction, particularly at lower doses.
In contrast, healthy muscle cells did not exhibit increased cell death in response to the combination of DOX and magnetic pulses, showing that non-cancerous tissues received better protection.
The researchers also found that decreasing TRPC1 levels or inhibiting its function nullified this effect, confirming the essential role of TRPC1 channels in this process. “Notably, enhancing TRPC1 levels resulted in increased DOX absorption, indicating that TRPC1 could serve as a promising therapeutic target for aggressive cancers,” said Mr. Vinesh Krishnan Sukumar, the study’s lead author and a PhD candidate at the NUS Centre for Cancer Research (N2CR) associated with NUS Yong Loo Lin School of Medicine.
“What’s encouraging is that this mechanism functions most effectively at lower drug concentrations, allowing us to effectively target cancer cells while minimizing the impact of chemotherapy on healthy tissues,” added Assoc Prof Franco-Obregón.
As breast cancer continues to be the leading cause of cancer-related deaths among women globally, developing new treatment strategies is imperative. “Most women undergoing chemotherapy experience side effects from the treatment, which can lead to reductions in drug doses or, in severe instances, early termination of treatment,” explained Assistant Professor Joline Lim, a member of the research team and Principal Investigator at N2CR. “Additionally, extended exposure to high-dose chemotherapy can lead to drug resistance. This targeted method offers an excellent opportunity to potentially enhance treatment success while maintaining the quality of life for patients.”
Expanding the possibilities of precision oncology
The magnetic-assisted method employed by the team addresses one of chemotherapy’s most significant challenges: its harmful effects on healthy tissues. By specifically increasing drug absorption in cancer cells, this approach could drastically cut down on the systemic side effects that many breast cancer patients endure. This improvement not only enhances treatment efficacy and quality of life but also encourages earlier interventions for those hesitant due to treatment-related side effects. The study further highlights the importance of biomarkers, like elevated TRPC1 expression, in revolutionizing cancer care through precision-driven treatments.
Future research will aim to implement these findings in clinical settings by directing magnetic field exposure precisely to tumors in patients. This would further validate the potential for reducing systemic DOX doses while maximizing localized drug delivery to cancer cells.
“Our method will be patented and is set to form the basis for a startup focused on breast cancer treatment. We are currently engaging with potential investors in Southeast Asia and the United States to transition this technology from research to practical application,” shared Assoc Prof Franco-Obregón.
