A group of drugs commonly used to treat erectile dysfunction may enhance the effect of chemotherapy in esophageal cancer, according to new research. Esophageal cancer affects the esophagus 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) located in the area. around the tumor.
While this research is in early discoveries, when combined with chemotherapy, PDE5 inhibitors may shrink some esophageal tumors more than chemotherapy alone could, addressing chemotherapy resistance, which is one of the biggest challenges in treating esophageal cancer. said Professor Tim Underwood of the University of Southampton.
Currently, this disease has much poorer outcomes and treatment options compared to other cancers, with only 1 in 10 patients surviving their disease for 10 years or more. Part of the reason for this is that it can be resistant to chemotherapy in many cases, with about 80 percent of people failing to respond.
Resistance to chemotherapy in esophageal cancer is influenced by the tumor’s microenvironment, the area where the tumor sounds. This consists of molecules, blood vessels and cells such as cancer-associated fibroblasts (CAFs), which are important for tumor growth.
It nourishes the tumor and can act as a protective sheath, preventing treatments such as chemotherapy from having an effect. “The chemotherapy-resistant properties of esophageal tumors leave many patients undergoing intensive chemotherapy that doesn’t work for them.
Finding a drug that is already safely prescribed to people every day could be a big step forward in tackling this difficult-to-treat disease,” said Underwood, lead author and professor of gastrointestinal surgery at the university. researchers wanted to identify the cells in the tumor’s microenvironment.
They found that levels of PDE5, an enzyme originally found in the wall of blood vessels, are higher in adenocarcinoma of the esophagus than in healthy esophageal tissue. High levels of PDE5 were also found in CAFs and the drug was found to suppress CAF activity.
They also tested a combination of PDE5i and standard chemotherapy on lab-grown artificial tumors. Of the 12 samples from patients whose tumors developed a poor response to chemotherapy in the clinic, 9 were sensitized to standard chemotherapy by targeting CAFs with PDE5i.
The researchers also tested the treatment on mice implanted with chemotherapy-resistant esophageal tumors and found that there were no adverse side effects to the treatment, and that chemotherapy combined with PDE5i shrank the tumors more than chemotherapy alone.