A reignited debate over the cell(s) of origin for glioblastoma and its clinical implications

Abstract

Glioblastoma (GBM) is the most common and lethal primary neoplasm in the central nervous system. Despite intensive treatment, the prognosis for patients with GBM remains poor, with a median survival of 14--16 months. 90% of GBMs are primary GBMs that are full-blown at diagnosis without evidences of a pre-existing less-malignant precursor lesion. Therefore, identification of the cell(s) of origin for GBM---the normal cell or cell type that acquires the initial GBM-promoting genetic hit(s)---is the key to the understanding of the disease etiology and the development of novel therapies. Neural stem cells and oligodendrocyte precursor cells are the two major candidates for the cell(s) of origin for GBM. Latest data from human samples have reignited the longstanding debate over which cells are the clinically more relevant origin for GBMs. By critically analyzing evidences for or against the candidacy of each cell type, we highlight the most recent progress and debate in the field, explore the clinical implications, and propose future directions toward early diagnosis and preventive treatment of GBMs.

Keywords

glioblastoma / cell(s) of origin / neural stem cells / oligodendrocyte precursor cells / subventricular zone / early diagnosis

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Acknowledgements

This work was supported by the National Key Research and Development Program of China, Stem Cell and Translational Research (No. 2017YFA0106500), Distinguished Young Scientists Program of Sichuan Province (No. 2019JDJQ0029), and Thousand Talents Program for Young Outstanding Scientists, China.

Compliance with ethics guidelines

Xiaolin Fan, Yanzhen Xiong, and Yuan Wang declare there is no conflict of interest. This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

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