4.6 Article

Glioblastoma-initiating cell heterogeneity generated by the cell-of-origin, genetic/epigenetic mutation and microenvironment

Journal

SEMINARS IN CANCER BIOLOGY
Volume 82, Issue -, Pages 176-183

Publisher

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcancer.2020.12.003

Keywords

Glioblastoma (GBM); GBM-initiating cells (GICs); Heterogeneity; Temozolomide (TMZ); Dihydroorotate dehydrogenase (DHODH)

Categories

Funding

  1. Grant-In-Aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Sci-ence and Technology of Japan.

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This article discusses the heterogeneity of cancer cells in Glioblastoma (GBM) and other malignant tumors, and explores how this heterogeneity is generated. The article also emphasizes the importance of addressing cell heterogeneity and presents solutions based on recent research findings.
Glioblastoma (GBM) and other malignant tumours consist of heterogeneous cancer cells, including GBMinitiating cells (GICs). This heterogeneity is likely to arise from the following: different sets of genetic mutations and epigenetic modifications, which GICs gain in the transformation process; differences in cells of origin, such as stem cells, precursor cells or differentiated cells; and the cancer microenvironment, in which GICs communicate with neural cells, endothelial cells and immune cells. Furthermore, considering that various types of GICs can be generated at different time points of the transformation process, GBM very likely consists of heterogeneous GICs and their progeny. Because cancer cell heterogeneity is responsible for therapy resistance, it is crucial to develop methods of reducing such heterogeneity. Here, I summarize how GIC heterogeneity is generated in the transformation process and present how cell heterogeneity in cancer can be addressed based on recent findings.

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