A drug best known for numbing the skin before minor medical procedures may hold unexpected promise in tackling one of the most aggressive childhood cancers.
Researchers investigating neuroblastoma – a cancer that primarily affects babies and children under five – have discovered that tetracaine, a long‑established local anaesthetic, can significantly suppress the cancer cells’ ability to invade surrounding tissue in laboratory experiments.
The study, published in Basic & Clinical Pharmacology & Toxicology, offers an intriguing demonstration of how a safe, widely used drug could potentially be repurposed to curb the spread of neuroblastoma. Although this research is still at an early stage, the findings add momentum to a rapidly growing field known as cancer neuroscience, which examines how the electrical properties of cancer cells influence disease progression.
The research team included scientists in the Dynamical Cell Systems Group at The Institute of Cancer Research, London. Visiting scientist and first author Dr Ece Selçuk, usually based at Istanbul Medeniyet University in Turkey, kindly carried out much of the experimental work as a volunteer. Other research costs were funded by the Pro Cancer Research Fund and The Institute of Cancer Research, which is both a research institute and a charity.
Cancer neuroscience and the CELEX model
At the heart of this research lies a biological mechanism called electrical excitability. Neuroblastoma arises from immature nerve cells, so it already has neuronal characteristics. Despite this, the research team found that the cancer appears to rely on a boost in electrical activity to become invasive.
This observation supports the CELEX (‘cellular excitability’) model, a theory proposing that many cancers gain their ability to invade and spread by upregulating tiny proteins called voltage‑gated sodium channels (VGSCs). VGSCs sit in the cell membrane and act like gates, controlling the influx of sodium ions to help generate electrical impulses. Although they are best known for their role in nerves and muscles, VGSCs are increasingly recognised as drivers of cancer aggressiveness.
Tetracaine is relevant to this model because local anaesthetics block VGSCs. In nerve cells, this prevents the transmission of pain signals. In cancer cells, researchers believe that it interferes with the electrical changes that support invasion and metastasis.
The new study is the first to test this concept in a cancer that already displays neuronal traits. Previously, researchers were unsure whether the CELEX model would hold true for neuroblastoma, or whether the disease’s pre‑existing electrical properties would make VGSC blockers less effective. Encouragingly, the results suggest that neuroblastoma cells may be just as reliant on electrical excitability as the other cancers previously studied.
From breast cancer clues to childhood cancer hopes
The team’s interest in VGSC‑blocking drugs was sparked, in part, by a 2023 breast cancer trial showing that using local anaesthesia during surgery significantly reduced the chance of disease recurrence. This unexpected finding prompted scientists to look more closely at whether anaesthetics might directly influence cancer cell behaviour.
Those clinical observations were mirrored by the new laboratory results in neuroblastoma, strengthening the argument that this class of drugs may have broad anti‑invasive effects across multiple tumour types.
What the study found
Working with human neuroblastoma cell lines, the researchers exposed the cancer cells to tetracaine and observed their behaviour using established laboratory assays designed to measure invasiveness. The results showed a marked suppression of invasive activity, suggesting that blocking VGSCs interrupts a critical mechanism used by neuroblastoma cells to spread.
Although this study does not guarantee that the same effect would occur in patients, it lays essential groundwork for future investigations. These may include verifying VGSC expression in tumour samples, correlating this expression with disease severity and survival, and expanding experiments into three‑dimensional models.
One ongoing project at the ICR aims to identify molecular signatures that would indicate which groups of patients would be most likely to benefit from these types of drugs. The researchers are also keen to test other VGSC‑blocking drugs – such as different local anaesthetics, anti‑epileptics and anti‑arrhythmics – which are already widely used for other conditions.
If these lines of evidence continue to converge, the research could pave the way towards a clinical trial. What’s more, neuroblastoma’s classification as a rare disease means that any trial showing promise could be fast‑tracked.
Hope for families worldwide
Neuroblastoma is relatively rare but devastating. In the UK, oncologists diagnose 80 to 100 new cases each year, while globally, there are an estimated 5,500 to 6,000 new cases annually.
Most deaths from neuroblastoma are caused by metastatic spread rather than the primary tumour. Any treatment capable of reducing invasion and metastasis could therefore make a significant difference to survival outcomes.
The long-term vision outlined by the researchers is particularly compelling. If further studies confirm the therapeutic potential of VGSC blockers, these drugs could eventually be used during surgery or as part of broader treatment regimens to reduce the likelihood of metastasis. As they include medications already approved for other conditions, clinical translation could be quicker than for newly developed drugs.
A promising direction, with more work ahead
Although early‑stage, the study validates the broader principle that manipulating cancer cell bioelectricity can influence disease behaviour. For a field still in its scientific adolescence, this represents valuable progress.
Professor Chris Bakal, Professor of Cancer Morphodynamics at The Institute of Cancer Research (ICR) and an author on the paper, said:
“We are seeing time and time again that cancer cells have different ‘electrical activity’ than normal cells. My own team is developing AI tools in order to see this electricity in living cancer cells and in patients. 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. I think if we can find which patients are most likely to respond, this could really open up therapeutic avenues.
“For families affected by neuroblastoma, even incremental scientific advances matter deeply. This latest finding – that a familiar numbing agent could one day help block the spread of a deadly childhood cancer – offers a hopeful glimpse into what the emerging discipline of cancer neuroscience might deliver in the years ahead.”
Co-author Mar Arias-Garcia, a Senior Scientific Officer in the Dynamical Cell Systems Group at the ICR, said:
“The promise is that by using VGSC‑blocking drugs, we could help suppress metastatic disease. Since metastasis is the main cause of death in neuroblastoma, this approach could significantly extend survival – even to the point of offering children the chance of a healthy lifespan.”
More work is needed to substantiate the evidence before any patient benefit can be realised, but the researchers are confident that the direction of travel is promising, and that a clinical trial is a realistic future goal.
Image credit: Gerd Altmann from Pixabay