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The Efficiency of Verteporfin as a Therapeutic Option in Pre-Clinical Models of Melanoma. | LitMetric

AI Article Synopsis

  • YAP and TAZ are proteins that promote tumor growth in various cancers, including melanoma, by interacting with transcription factors called TEAD.
  • Verteporfin, a drug used for eye conditions, has been found to reduce YAP and TAZ levels in lab tests but is being studied for its potential to inhibit their cancer-promoting activity without needing light activation.
  • In tests on human melanoma cell cultures and a mouse model designed to mimic human melanoma, Verteporfin effectively lowered YAP and TAZ levels, but it did not prevent the initiation or progression of melanoma, suggesting its limitations as a targeted treatment in clinical scenarios.

Article Abstract

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, Braf; Tyr-CreERT2; Pten, 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329844PMC
http://dx.doi.org/10.7150/jca.27472DOI Listing

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