- According to the authors, approximately 80% of people with esophageal cancer do not respond to chemotherapy.
- The treatment, already authorized worldwide, generates few side effects, even with high doses.
- In 2018, more than 5,400 new cases of esophageal cancer were identified in France.
“The prognosis for esophageal cancer is grim.”, recalls the French National Society of Gastroenterology. A new study published in the specialized journal Cell Reports Medicine, could improve the chances of survival for those affected. Scientists from the British Cancer Research Center have discovered that a drug used against erectile dysfunction can enhance the effects of chemotherapy in the case of esophageal cancer.
Resistance to chemotherapy
The treatment, known as a PDE5 inhibitor, can block chemotherapy resistance by targeting cells called cancer-associated fibroblasts (CAFs) located in the area around the tumour. These contribute to the growth of the tumor by feeding it and covering it, which blocks the action of treatments such as chemotherapy. Cancer Research UK researchers first found that levels of PDE5, an enzyme found in the wall of blood vessels, are higher in esophageal adenocarcinoma than in healthy tissue. High levels of PDE5 were then found in CAFs, and high expression of this enzyme is associated with lower overall survival.
After this first discovery, the researchers tested a PDE5 inhibitor, used in the treatment of erectile dysfunction. “Developing new cancer drugs is hugely important, but doing it from scratch is a difficult process, and many fail along the way.recalls Michelle Mitchell, director general of Cancer Research UK. We were keen to determine whether existing drugs, approved for other diseases, can be effective in treating cancer.”
To test its action in esophageal cancer, scientists took samples of tumor cells from 15 biopsies from eight patients to create artificial tumors grown in the laboratory. On them, the scientists tested a combination of PDE5 and standard chemotherapy. Of the 12 patient samples whose tumors initially did not respond to chemotherapy, nine became responsive to standard chemotherapy using this method.
For the authors, these results are proof that “PDE5 inhibitors plus chemotherapy could shrink some esophageal tumors more than chemotherapy alone, addressing resistance to chemotherapy, which is one of the main challenges in treating esophageal cancer.”. The next step in their work will be a phase I and II clinical trial to test a PDE5 inhibitor in combination with chemotherapy in patients with advanced esophageal cancer.