Medulloblastoma targeted therapy: From signaling pathways heterogeneity and current treatment dilemma to the recent advances in development of therapeutic strategies

Qiyue Wang; Xiaofei Xin; Qihao Dai; Mengjuan Sun; Jinhua Chen; Ebrahim Mostafavi; Yan Shen; Xueming Li

doi:10.1016/j.pharmthera.2023.108527

Medulloblastoma targeted therapy: From signaling pathways heterogeneity and current treatment dilemma to the recent advances in development of therapeutic strategies

Pharmacol Ther. 2023 Oct:250:108527. doi: 10.1016/j.pharmthera.2023.108527. Epub 2023 Sep 12.

Authors

Qiyue Wang¹, Xiaofei Xin², Qihao Dai¹, Mengjuan Sun², Jinhua Chen², Ebrahim Mostafavi³, Yan Shen⁴, Xueming Li⁵

Affiliations

¹ School of Pharmaceutical Science, Nanjing Tech University, Nanjing 211816, China.
² Center for Research Development and Evaluation of Pharmaceutical Excipients and Generic Drugs, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
³ Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: ebimsv@stanford.edu.
⁴ Center for Research Development and Evaluation of Pharmaceutical Excipients and Generic Drugs, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China. Electronic address: shenyan@cpu.edu.cn.
⁵ School of Pharmaceutical Science, Nanjing Tech University, Nanjing 211816, China. Electronic address: xuemingli@njtech.edu.cn.

PMID: 37703952
DOI: 10.1016/j.pharmthera.2023.108527

Abstract

Medulloblastoma (MB) is a major pediatric malignant brain tumor that arises in the cerebellum. MB tumors exhibit highly heterogeneous driven by diverse genetic alterations and could be divided into four major subgroups based on their different biological drivers and molecular features (Wnt, Sonic hedgehog (Shh), group 3, and group 4 MB). Even though the therapeutic strategies for each MB subtype integrate their pathogenesis and were developed to focus on their specific target sites, the unexpected drug non-selective cytotoxicity, low drug accumulation in the brain, and complexed MB tumor microenvironment still be huge obstacles to achieving satisfied MB therapeutic efficiency. This review discussed the current advances in modern MB therapeutic strategy development. Through the recent advances in knowledge of the origin, molecular pathogenesis of MB subtypes and their current therapeutic barriers, we particularly reviewed the current development in advanced MB therapeutic strategy committed to overcome MB treatment obstacles, focusing on novel signaling pathway targeted therapeutic agents and their combination discovery, advanced drug delivery systems design, and MB immunotherapy strategy development.

Keywords: Blood-brain barrier; Drug delivery platforms; Immunotherapy; Medulloblastoma; Targeting therapy strategies.

Publication types

Review