Luckily drugs that target PDE5 already exist, but they might not be what you expect…
Drugs like Viagra, used to treat erectile dysfunction, are PDE5 inhibitors.
The researchers found that they could use PDE5 inhibitors to make oesophageal tumour samples from patients that had previously shown a poor response to treatment more sensitive to the effects of chemotherapy.
Although this is early discovery research, PDE5 inhibitors combined with chemotherapy may be able to shrink some oesophageal tumours more than chemotherapy could alone. They could be a way to tackle chemotherapy resistance, which is one of the major challenges in treating oesophageal cancer.
4. Studying precancer to prevent oesophageal cancer
By looking more closely at how cancers start, we can work out how to stop them.
That’s why Cancer Grand Challenges team eDyNAmiC are investigating how DNA changes lead to cancer.
Specifically, they’re looking at extrachromosomal DNA (ecDNA): strange rings of DNA that aren’t where they’re supposed to be in our cells. These are often associated with cancer, and it was thought that they were a late effect of the disease. But last year that all changed.
In a collaboration with Professor Fitzgerald’s OCCAMS team, eDyNAmiC used patient data to look directly at the changes that took place as Barrett’s oesophagus transitioned to oesophageal cancer. Then, they compared those changes to what happened in cases that didn’t become malignant.
That new approach paid off.
Surprisingly, the team discovered that people can have ecDNAs in abnormal oesophageal cells that aren’t cancerous. But this changes how the cells behave.
Once ecDNA appears, the chances of Barrett’s oesophagus turning into oesophageal cancer get much higher. That suggests that, rather than being a late effect of cancer, ecDNA might be a driving force behind it.
So, what does this really mean?
Extrachromosomal DNA appears in half of all cancer types. It’s a feature of many of the most aggressive and hard-to-treat tumours.
Now, because we can see what ecDNA is doing, we can work out specific ways to stop it. And, as eDyNAmiC begin to focus on targeting ecDNA with drugs, this new way of understanding cancer could become a way to intercept and prevent it, too.