The SHH/GLI signaling pathway: a therapeutic target for medulloblastoma. (1st November 2020)

• Record Type: Journal Article
• Authors: Lospinoso Severini, Ludovica; Ghirga, Francesca; Bufalieri, Francesca; Quaglio, Deborah; Infante, Paola; Di Marcotullio, Lucia
• Is Part Of: Expert opinion on therapeutic targets. Volume 24:Number 11(2020:Nov.)
• Page Start: 1159
• Page End: 1181
• Publication Date: 2020-11-01
• Subjects: Cancer -- drug discovery -- gli -- hedgehog pathway -- immunotherapy -- medulloblastoma -- multitarget -- small molecules -- smo -- therapeutic target; Drugs -- Research -- Periodicals; 615.072
• DOI: 10.1080/14728222.2020.1823967
• Languages: English
• ISSNs: 1744-7631

Abstract

ABSTRACT: Introduction: Medulloblastoma (MB) is a heterogeneous tumor of the cerebellum that is divided into four main subgroups with distinct molecular and clinical features. Sonic Hedgehog MB (SHH-MB) is the most genetically understood and occurs predominantly in childhood. Current therapies consist of aggressive and non-targeted multimodal approaches that are often ineffective and cause long-term complications. These problems intensify the need to develop molecularly targeted therapies to improve outcome and reduce treatment-related morbidities. In this scenario, Hedgehog (HH) signaling, a developmental pathway whose deregulation is involved in the pathogenesis of several malignancies, has emerged as an attractive druggable pathway for SHH-MB therapy. Areas covered: This review provides an overview of the advancements in the HH antagonist research field. We place an emphasis on Smoothened (SMO) and glioma-associated oncogene homolog (GLI) inhibitors and immunotherapy approaches that are validated in preclinical SHH-MB models and that have therapeutic potential for MB patients. Literature from Pubmed and data reported on ClinicalTrial.gov up to August 2020 were considered. Expert opinion: Extensive-omics analysis has enhanced our knowledge and has transformed the way that MB is studied and managed. The clinical use of SMO antagonists has yet to be determined, however, future GLI inhibitors and multitargeting approaches are promising.