Verteporfin (VP) has long been clinically used to treat
age-related macular degeneration (AMD) through
photodynamic therapy (
PDT). Recent studies have reported a significant anti-
tumor effect of VP as well. Yes-associated
protein (YAP) is a pro-tumorigenic factor that is aberrantly expressed in various
cancers and is a central effector of the Hippo signaling pathway that regulates organ size and
tumorigenesis. VP can inhibit YAP without photoactivation, along with suppressing autophagy, and downregulating germinal center
kinase-like
kinase (GLK) and STE20/SPS1-related
proline/
alanine-rich
kinase (SPAK). In addition, VP can induce mitochondrial damage and increase the production of
reactive oxygen species (ROS) upon photoactivation, and is an effective
photosensitizer (PS) in anti-
tumor PDT. We have reviewed the direct and adjuvant therapeutic action of VP as a PS, and its YAP/
TEA domain (TEAD)-dependent and independent pharmacological effects in the absence of light activation against
cancer cells and solid
tumors. Based on the present evidence, VP may be repositioned as a promising anti-
cancer chemotherapeutic and adjuvant drug.