Erectile dysfunction drugs could help in the treatment of esophageal cancer (Viagra)

Medical Xpress / Cancer Research UK / Cell Reports Medicine ^ | June 21, 2022 | Benjamin P. Sharpe et al

[ConservativeMind]

A group of drugs commonly used to treat erectile dysfunction may be able to boost the effect of chemotherapy in esophageal cancer, according to new research.

This research found the drugs, known as PDE5 inhibitors can reverse chemotherapy resistance by targeting cells called cancer-associated fibroblasts (CAFs) residing in the area surrounding the tumor.

Although this is early discovery research, PDE5 inhibitors combined with chemotherapy may be able to shrink some esophageal tumors more than chemotherapy could alone, tackling chemotherapy resistance, which is one of the major challenges in treating esophageal cancer.

The researchers found that levels of PDE5, an enzyme originally found in the wall of blood vessels are higher in esophageal adenocarcinoma compared with healthy esophageal tissue. High levels of PDE5 were found in CAFs within the tumor 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.

Following this, the researchers tested a PDE5 inhibitor, PDE5i, on CAFs from esophageal tumors. They found that PDE5i were able to suppress CAF activity and make them look more like normal fibroblasts.

Next, collaborating researchers at the University of Nottingham took samples of tumor cells from 15 tissue biopsies from eight patients, and used them to create lab-grown artificial tumors. They tested a combination of PDE5i and standard chemotherapy on the tumors. Of the 12 samples from patients whose tumors 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 esophageal tumors and found that there were no adverse side effects to the treatment, and that chemotherapy combined with PDE5i shrunk the tumors more than chemotherapy alone.

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