Yes Associated
Protein 1 (YAP) and Transcriptional coactivator with PDZ-Binding Motif (TAZ) have gained notoriety for their ability to drive
tumor initiation and progression in a wide variety of
cancers, including
melanoma. YAP and TAZ act as drivers of
melanoma through its interaction with the TEAD family of
transcription factors.
Verteporfin is a benzoporphyrin derivative that is used clinically for photodynamic treatment of
macular degeneration. Recently it has emerged as a potential inhibitor of YAP/TAZ-TEAD interaction independent of light activation. In this study we determine if
verteporfin has clinical potential by testing this compound on human
melanoma cell cultures and in a clinically significant mouse model, BrafCA; Tyr-CreERT2; Ptenf/f, which parallels human
melanoma in terms of
disease progression, genetics, and histopathology. In culture,
Verteporfin treatment induces a rapid drop in YAP and TAZ
protein levels and cell numbers. In the transgenic model, utilizing
drug levels that correspond to previously determined safe doses in human patients and with a dosing regimen calculated in this study,
Verteporfin did not inhibit
melanoma initiation or progression in comparison to mock treated controls. Taken together, our study suggests that although
Verteporfin induces YAP/TAZ degradation in
melanoma cell lines,
Verteporfin was not effective as a YAP/TAZ-TEAD specific inhibitor of
melanoma in our studies that aimed to mimic conditions found in clinic in terms of treatment regimen and disease model.