A Groundbreaking Study from ICR London on Tetracaine's Potential

Researchers at the Institute of Cancer Research (ICR), London, a leading postgraduate university specialising in oncology and part of the University of London, have uncovered a promising avenue for treating one of the most aggressive childhood cancers. Their recent laboratory study demonstrates that tetracaine, a long-established local anaesthetic commonly used to numb skin before minor medical procedures, significantly suppresses the invasive behaviour of neuroblastoma cells. This discovery highlights the potential of repurposing existing, safe drugs to combat cancer metastasis, a critical challenge in paediatric oncology.

The work, led by Professor Chris Bakal's Dynamical Cell Systems Group at ICR, builds on the emerging field of cancer neuroscience. This interdisciplinary area explores how cancer cells hijack neuronal-like electrical properties to drive invasion and spread. For families facing neuroblastoma diagnoses, such incremental advances offer real hope, potentially paving the way for less toxic treatments that could extend survival and improve quality of life.

Understanding Neuroblastoma: A Formidable Childhood Cancer

Neuroblastoma is a rare and often aggressive cancer that primarily affects infants and young children under the age of five. It originates from immature nerve cells, typically in the adrenal glands, abdomen, or near the spine, and is characterised by its neuronal features. In the United Kingdom, approximately 80 to 100 new cases are diagnosed annually, contributing to the roughly 1,645 childhood cancers (ages 0-14) reported each year. Globally, the figure rises to 5,500-6,000 cases.

While overall five-year survival for childhood cancers in the UK stands at around 84%, neuroblastoma lags behind at approximately 70% in England. The primary reason for poor outcomes is metastasis—the spread of cancer cells from the primary tumour to distant sites like bones, liver, or lymph nodes. Even with intensive multimodal therapy involving surgery, chemotherapy, radiation, and immunotherapy, high-risk cases remain difficult to cure. This underscores the urgent need for innovative strategies targeting metastasis.

The Research Team and ICR's Expertise in Paediatric Oncology

The study was spearheaded by Dr. Ece Selçuk, a visiting scientist from Istanbul Medeniyet University, who conducted much of the experimental work on a voluntary basis. Co-authors include Vicky Bousgouni, Mar Arias-Garcia (Senior Scientific Officer), and Professor Chris Bakal, Professor of Cancer Morphodynamics at ICR. The team's efforts were supported by funding from the Pro Cancer Research Fund and ICR's own resources.

ICR London stands at the forefront of UK higher education in cancer research, ranking highly in biological sciences and hosting specialised postgraduate programmes. Its Paediatric Solid Tumour Biology and Therapeutics Group, led by Professor Louis Chesler, complements this work with advanced models for neuroblastoma spread and genetic studies. ICR's collaborations, such as with the Royal Marsden NHS Foundation Trust, exemplify how UK universities drive translational research from lab to clinic.

This study exemplifies the vital role of specialised UK institutions like ICR in fostering innovative research environments, attracting international talent, and training the next generation of cancer scientists through PhD and MD(Res) programmes.

The Science Behind Tetracaine's Anti-Invasive Effects

At the heart of the discovery is the cancer excitability and local excitability (CELEX) model, which posits that metastatic cancer cells upregulate voltage-gated sodium channels (VGSCs)—proteins typically found in excitable cells like neurons—to enhance their invasiveness. VGSCs allow sodium ions to flow into cells, altering membrane potential and promoting migration and tissue penetration.

Tetracaine, an ester-type local anaesthetic, blocks these VGSCs by binding to their inner pore, stabilising the channel in a non-conducting state. In the experiments, human neuroblastoma cell lines were exposed to tetracaine concentrations of 25-50 μM—levels achievable clinically without toxicity. Standard invasion assays showed a marked reduction in cell invasiveness, validating VGSC targeting without significantly affecting proliferation or viability. This is the first application of the CELEX model to neuroblastoma, despite its inherent neuronal traits.

The full study details are available in the peer-reviewed paper published in Basic & Clinical Pharmacology & Toxicology.

Lab Findings and Methodological Rigor

Using established in vitro assays, the ICR team quantified invasion by observing how neuroblastoma cells traversed matrix barriers mimicking tissue. Tetracaine treatment dose-dependently curtailed this, with statistical significance (p < 0.05). Controls confirmed specificity to VGSC blockade, as other ion channel effects were minimal. The study employed multiple cell lines to ensure reproducibility across neuroblastoma subtypes.

Professor Bakal noted, "It was very validating to see just how effectively tetracaine reduced invasive behaviours in neuroblastoma cells. This kind of response from a clinically used, non-toxic drug is very promising." Such rigorous preclinical data positions this for rapid progression to patient models.

Broader Context: Cancer Neuroscience and VGSC Blockers

Cancer neuroscience is revolutionising oncology by revealing how tumours exploit bioelectric signals. Pioneered by UK researchers like Professor Mustafa Djamgoz at Imperial College London, VGSC upregulation correlates with metastasis in breast, prostate, and other cancers. A 2023 clinical trial showed local anaesthesia during breast cancer surgery reduced recurrence, inspiring ICR's neuroblastoma application.

Other VGSC blockers, including anti-epileptics and anti-arrhythmics, warrant exploration. ICR is developing AI tools to visualise cancer cell electricity in vivo, potentially identifying responders via molecular signatures.

Implications for Treatment and Clinical Translation

Metastasis drives 90% of neuroblastoma deaths; blocking it could transform outcomes. Tetracaine's safety profile and orphan drug status for rare cancers facilitate fast-tracked trials—perhaps perioperative administration or combination therapy. Mar Arias-Garcia emphasised, "By using VGSC-blocking drugs, we could help suppress metastatic disease... offering children the chance of a healthy lifespan."

Challenges include verifying VGSC expression in patient tumours and testing in 3D organoids or xenografts. Success could extend to other paediatric solid tumours studied at ICR, like medulloblastoma.

ICR's Pivotal Role in UK Childhood Cancer Research

ICR leads UK efforts in paediatric oncology, with projects like SMPaeds using liquid biopsies for precision medicine. Professor Chesler's group advances neuroblastoma models and ecDNA detection. Funded by CRUK and charities, ICR's REF 2021 ranking underscores its excellence, training PhDs who drive innovations.

This positions UK higher education as a global hub for cancer neuroscience, attracting funding and talent.

UK Landscape: Statistics, Challenges, and Progress

UK childhood cancer incidence rose 8% since 2000s, with 45% in 0-4 year-olds. Despite 84% survival, disparities persist—neuroblastoma lags Europe-wide. Early diagnosis and metastasis prevention are key. Charities like Children with Cancer UK support ICR, emphasising research investment.

Government and EU funding bolster UK universities, but calls grow for more in rare cancers.

Stakeholder Perspectives and Patient Impact

Families and survivors advocate for such research. Pro Cancer Research Fund enabled this voluntary effort. Experts like Bakal stress, "For families affected by neuroblastoma, even incremental scientific advances matter deeply." This aligns with UK strategies for equitable access to innovative therapies.

Ethical considerations prioritise minimal toxicity for children, making repurposed drugs ideal.

Photo by National Cancer Institute on Unsplash

Future Outlook: From Lab to Lifesaving Therapies

Next steps: Validate in patient samples, advance to animal models, and launch trials. ICR's AI and liquid biopsy tools accelerate this. As cancer neuroscience matures, VGSC blockers could redefine metastasis management across cancers. UK higher education's leadership promises faster cures, benefiting global patients.

For aspiring researchers, ICR exemplifies career opportunities in cutting-edge oncology. Explore research positions to contribute.