A New Player in Neuroblastoma: YAP and Its Role in the Neuroblastoma Microenvironment

SIMPLE SUMMARY: Neuroblastoma is the most common extra-cranial solid tumor of childhood arising from the developing sympathetic neuroblast. Despite intense multimodal therapy, more than half of patients with high-risk neuroblastoma relapse with incurable disease. The Yes-Associated Protein (YAP) has been shown to play a critical role in many types of cancers, including neuroblastoma. YAP has also been recently highlighted as an important regulator of the tumor microenvironment (TME) that can affect cancer growth and response to therapies. Here, we focus on YAP and its role in neuroblastoma and the TME that underscores the therapeutic potential of inhibiting YAP in this highly aggressive pediatric solid tumor. ABSTRACT: Neuroblastoma is the most common extra-cranial pediatric solid tumor that accounts for more than 15% of childhood cancer-related deaths. High risk neuroblastomas that recur during or after intense multimodal therapy have a <5% chance at a second sustained remission or cure. The solid tumor microenvironment (TME) has been increasingly recognized to play a critical role in cancer progression and resistance to therapy, including in neuroblastoma. The Yes-Associated Protein (YAP) in the Hippo pathway can regulate cancer proliferation, tumor initiation, and therapy response in many cancer types and as such, its role in the TME has gained interest. In this review, we focus on YAP and its role in neuroblastoma and further describe its demonstrated and potential effects on the neuroblastoma TME. We also discuss the therapeutic strategies for inhibiting YAP in neuroblastoma.