Targeting the Hippo/YAP Pathway: A Promising Approach for Cancer Therapy and Beyond

Cancer represents a growing cause of death and a threat to public health worldwide; thus, there is an urgent need to understand its pathological mechanism and design effective therapies. The Hippo pathway regulates diverse cellular processes under physiological conditions; however, its dysregulation is associated with several types of cancer, including lung, pancreatic, colorectal, breast, and prostate cancer. Consequently, compounds targeting deregulated Hippo components represent potential treatments for a broad spectrum of cancers. Nonetheless, currently, there is limited information integrating the growing evidence of this potential. Therefore, the review's objective is to provide insight into the potential efficacy of targeting the Hippo/yes-associated protein (YAP) pathway for cancer therapy. First, we describe the molecular mechanisms of the Hippo signaling pathway in physiological conditions and several cancer types. We then provide an overview of natural products and synthetic compounds targeting this pathway, highlighting their potential applications in treating diverse cancers. We also discuss relevant preclinical and clinical studies of compounds targeting the Hippo pathway in cancer. Finally, we summarize our findings and offer recommendations for future research. This review emphasizes the role of the Hippo/YAP pathway in cancer and the potential of natural products and synthetic compounds targeting this pathway for cancer treatment.