Some head and neck cancer cells initially respond to targeted therapy, but surprisingly quickly find new ways to survive. Researchers are investigating exactly how these cells evade targeted drugs such as cetuximab, and, in particular, how clever combination therapies can overcome this resistance.
The hidden consequences of smoking and drinking
A cigarette after dinner, a drink at a pub: for many, these are everyday habits. But those who smoke or drink alcohol for many years run a higher risk that these habits will leave their mark in a place few people ever think about: deep inside the cells of the throat and mouth.
Smoking and excessive alcohol use are amongst the leading causes of head and neck cancer. Every year, hundreds of thousands of people worldwide receive this diagnosis. The impact on daily life is often significant: speaking and swallowing become difficult or may be permanently affected. Despite intensive treatments, survival rates unfortunately remain limited.
Treatment often consists of a combination of surgery, chemotherapy and/or radiotherapy. Chemotherapy and radiotherapy in particular aren’t very specific: they target not only cancer cells, but also healthy cells. This makes treatment demanding and burdensome for patients.
What is head and neck cancer?
Head and neck cancer is a collective term for various types of cancer in the neck or head. The best-known form is probably throat cancer, but laryngeal cancer, salivary gland cancer, tongue cancer and mouth cancer also fall under this category.
Targeted therapies aren’t always the solution
Fortunately, scientific research isn’t standing still. In recent years, researchers have made major strides towards new, targeted therapies that focus on specific cancer cells. One example is cetuximab, a drug used in the treatment of head and neck cancer. However, even this smart therapy encounters a persistent challenge. Many tumours respond only temporarily or not at all, because they become resistant to cetuximab.
Tumour cells fight back against treatment
Dr Hannah Zaryouh of the Centre for Oncological Research at the University of Antwerp studies how head and neck cancer cells respond to cetuximab. At first, the drug appears to do its job.
Under the microscope, we see that tumour cell growth slows down and some cells even die. But then something frustrating and fascinating happens. The cancer cells don’t simply give up. They fight back by activating alternative proteins and signalling pathways that help them survive and continue to grow. By opening up these new survival routes, they can keep growing as if the blockade had never existed. This adaptability is what makes cancer so difficult to treat, but it also creates opportunities.
Zaryouh's research therefore focuses on one central question: how can we prevent head and neck cancer cells from escaping cetuximab?
Instead of targeting tumour cells through a single route, we aim to hit several weak spots at once.
Smart combination therapy offers new opportunities
‘The answer doesn’t lie in one new miracle drug, but in smart combinations,’ says Hannah. ‘Instead of targeting tumour cells through a single route, we aim to hit several weak spots at once.’ This is why, in her research, Hannah combines cetuximab with other compounds that specifically block these alternative survival routes. In the laboratory, she tests whether this smart combination therapy can make cancer cells responsive to cetuximab again. ‘In this way, we hope to limit the tumour’s room to manoeuvre and stay one step ahead of resistance.’
Although this research is still entirely laboratory-based, it provides an important foundation for future treatment strategies. The goal is clear: to develop effective therapies that work for longer and are less burdensome for patients. Understanding how cancer learns to escape is the first step in fighting back and, ultimately, defeating the disease.