A group of drugs commonly used to treat erectile dysfunction may be able to boost the effect of chemotherapy in oesophageal cancer, according to new research funded by Cancer Research UK and the Medical Research Council.
This research, published today (Tuesday) in Cell Reports Medicine, found that the drugs, known as PDE5 inhibitors can reverse chemotherapy resistance by targeting cells called cancer-associated fibroblasts (CAFs) residing in the area surrounding the tumour.
Although this is early discovery research, PDE5 inhibitors combined with chemotherapy may be able to shrink some oesophageal tumours more than chemotherapy could alone, tackling chemotherapy resistance, which is one of the major challenges in treating oesophageal cancer.
Oesophageal cancer affects the food pipe that connects your mouth to your stomach, and while it is a relatively rare cancer, the UK has one of the higher rates in the world, with 9,300* new oesophageal cancer cases in the UK every year**.
Currently this disease has much poorer outcomes*** and treatment options compared to other cancers, with around just 1 in 10 patients surviving their disease for 10 years or more. Part of the reason for this is that, in many cases, it can be resistant to chemotherapy, with around 80% of people not responding****.
Resistance to chemotherapy in oesophageal cancer is influenced by the tumour microenvironment, the area that sounds the tumour. This is made up of molecules, blood vessels, and cells such as cancer associated fibroblasts (CAFs), which are important for tumour growth. It feeds the tumour and can act as a protective cloak, preventing treatments like chemotherapy from having an effect.
The team of researchers led by Professor Tim Underwood at the University of Southampton wanted to identify the cells in the tumour microenvironment which protects the tumour from treatment so they could target them.
The researchers found that levels of PDE5, an enzyme originally found in the wall of blood vessels are higher in oesophageal adenocarcinoma compared with healthy oesophageal tissue. High levels of PDE5 were found in CAFs within the tumour microenvironment. They also found that high expression of PDE5 is associated with worse overall survival, suggesting that PDE5 would be an effective target for treatment.