Drug Repurposing Revealed Abemaciclib and Palbociclib as Inhibitor of Phosphodiesterase-5 (PDE5) in Cancer-Associated Fibroblasts Paving the Way for the Treatment of Breast Cancer

Abstract

Background: A common element of the tumor microenvironment, cancer-associated fibroblasts play a major role in the development of breast cancer via a variety of pathways. Studies show that cancer-associated fibroblasts over express phosphodiesterase-5 in comparison to normal fibroblasts and that this overexpression is linked to increased fibroblast activation and a more aggressive CAF phenotype. High PDE5 levels in CAFs contribute to the remodeling of the extracellular matrix, increased secretion of pro-tumorigenic factors and suppression of anti-tumor immune responses. Materials and Methods: Targeting PDE5 in CAFs thus offers a convincing method to interfere with these cells