Therapeutic opportunities for cancers presented by natural and synthetic compounds targeting the Hippo signaling pathway

Abstract

A new trend in anti-cancer treatments through the disruption of the YAP-TEAD protein-protein interaction complex is recognized. YAP has been tipped as a key modulator of the Hippo signaling pathway. Binding of YAP to its transcription factor TEAD can lead to disease progression as it drives cell-proliferation and triggers anti-apoptosis signaling. Recent studies have uncovered promising activities of various small molecules for regulating components of the Hippo signaling pathway. By using a structural elucidation and computational approach, some small molecules are able to bind on the YAP-TEAD interaction interface and inhibit the Hippo pathway. This review highlights our current understanding of how natural and synthetic molecules regulate Hippo signaling activity and suggests how phytochemical compounds available today can target the YAP-TEAD protein interaction complex to eradicate cancer cells.