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.Oesophageal cancer affects the food pipe that connects the mouth to the stomach.
The research, published in the journal 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, said Professor Tim Underwood at the University of Southampton.
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 per cent 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 chemotherapy resistant properties of oesophageal tumours mean that many patients undergo intensive chemotherapy that won't work for them.
Finding a drug, which is already safely prescribed to people every day, could be a great step forward in tackling this hard-to-treat disease," said Underwood, lead author and Professor of Gastrointestinal Surgery at the varsity.The team of researchers wanted to identify the cells in the tumour microenvironment.
They 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 also found in CAFs, and the drug was shown to suppress CAF activity.
Further, they tested a combination of PDE5i and standard chemotherapy on lab-grown artificial tumours. Of the 12 samples from patients whose tumours developed a poor response to chemotherapy in the clinic, 9 were made sensitive to standard chemotherapy by targeting CAFs with PDE5i.
The researchers also tested the treatment on mice implanted with chemotherapy resistant oesophageal tumours and found that there were no adverse side effects to the treatment, and that chemotherapy combined with PDE5i shrunk the tumours more than chemotherapy alone.