Targeting the Sonic Hedgehog Signaling Pathway of Cancer Stem Cells to Treat Glioblastoma

Jiaying Liu
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Abstract

Glioblastoma is an aggressive malignant brain tumor, and its five-year relative survival rate for patients is only 6.8 percent. In addition, almost all glioblastomas recur even after intensive treatments including surgery, radiation and chemotherapy, which are believed to be attributed to cancer stem cells (CSCs), a small population of cells existing in a tumor with ability to self-renewal and differentiation. Of multiple signaling pathways, sonic hedgehog signaling is one critical pathway involved in CSCs regulation. Therefore, targeting the sonic hedgehog signaling represents a novel therapy to treat glioblastomas, and significant efforts have been made in recent years to develop the sonic hedgehog signaling inhibitor drugs. This article specifically focuses on recent advances in the sonic hedgehog signaling inhibitor drug development by targeting multiple components of the signaling cascade including sonic hedgehog ligand, Smoothened (SMO) and GLI. Those inhibitors hold a great promise to destroy glioblastoma CSCs and prevent and treat tumor recurrence in the future.
靶向肿瘤干细胞Sonic Hedgehog信号通路治疗胶质母细胞瘤
胶质母细胞瘤是一种侵袭性恶性脑肿瘤,其患者的5年相对存活率仅为6.8%。此外,几乎所有的胶质母细胞瘤即使在手术、放疗和化疗等强化治疗后也会复发,这被认为是由于肿瘤干细胞(cancer stem cells, CSCs),肿瘤中存在的一小群具有自我更新和分化能力的细胞。在多种信号通路中,sonic hedgehog信号通路是参与CSCs调控的重要途径之一。因此,靶向sonic hedgehog信号是治疗胶质母细胞瘤的一种新疗法,近年来人们在开发sonic hedgehog信号抑制剂药物方面做了大量工作。本文重点介绍了声波刺猬信号抑制剂药物的最新进展,该药物针对信号级联的多种成分,包括声波刺猬配体、Smoothened (SMO)和GLI。这些抑制剂在破坏胶质母细胞瘤CSCs和预防和治疗肿瘤复发方面具有很大的前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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