Targeting protein folding in N‐Myc‐driven medulloblastoma

• Published in: Molecular oncology Vol. 17; no. 3; pp. 387 - 389
• Main Authors: Valinciute, Gintvile, Roussel, Martine F.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.03.2023; John Wiley and Sons Inc; Wiley
• Subjects: Cancer; Cerebellar Neoplasms - genetics; Cerebellar Neoplasms - metabolism; chaperones; Commentaries; Conflicts of interest; EIF4E; Hedgehog protein; Hedgehog Proteins - metabolism; Hedgehog Signalling; Homeostasis; Hsp70; Hsp70 protein; Humans; Kinases; Medulloblastoma; Medulloblastoma - genetics; Medulloblastoma - metabolism; mTOR Signalling; Myc protein; N-Myc Proto-Oncogene Protein - metabolism; N‐Myc; Pediatric Cancer; Pediatrics; Protein Folding; protein translation; Signal Transduction; Stem cells; Therapeutic targets; Translational Regulation; Tumors; N-Myc; protein translation; Hsp70; medulloblastoma; EIF4E; chaperones
• ISSN: 1574-7891; 1878-0261
• DOI: 10.1002/1878-0261.13395

Selective targeting of N‐Myc‐driven Sonic hedgehog (SHH) medulloblastoma has been a challenge for many years and, despite decades of research, few targeted therapy opportunities exist. Recently, Kuzuoglu‐Ozturk et al. characterized the translatome of N‐Myc‐driven medulloblastoma as a promising therapeutic target. The study showed that N‐Myc controls a subset of members of the protein folding machinery that could be inhibited pharmacologically and validated a subset of Hsp70 functions as required for medulloblastoma progression in vitro and in vivo. A new study by Kuzuoglu‐Ozturk et al. identified a novel therapeutic vulnerability in N‐Myc‐driven Sonic hedgehog medulloblastoma. Selective translation of protein homeostasis pathways, including protein folding machinery components, drives tumour cell response to proteotoxic stress. Targeting the Hsp70 co‐chaperone leaves cells vulnerable to the proteotoxic stress induced by N‐Myc overexpression and inhibits N‐Myc‐driven medulloblastoma proliferation.