Therapy targets in glioblastoma and cancer stem cells: lessons from haematopoietic neoplasms

Journal of Cellular and Molecular Medicine

Maria Linda Cruceru¹  Monica Neagu³  Jean-Baptiste Demoulin² 

[1] Department of Cellular and Molecular Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania;MEXP Unit, de Duve Institute, Université catholique de Louvain, Brussels, Belgium;Immunobiology Department, National Institute of Pathology “Victor Babeş”, Bucharest, Romania

关键词: glioblastoma cancer stem cell;    cell surface markers;    signalling pathways;    haematopoietic stem cells;    leukaemia;   

DOI  :  10.1111/jcmm.12122

来源: Wiley

【 摘 要 】

Abstract

Despite intense efforts to identify cancer-initiating cells in malignant brain tumours, markers linked to the function of these cells have only very recently begun to be uncovered. The notion of cancer stem cell gained prominence, several molecules and signalling pathways becoming relevant for diagnosis and treatment. Whether a substantial fraction or only a tiny minority of cells in a tumor can initiate and perpetuate cancer, is still debated. The paradigm of cancer-initiating stem cells has initially been developed with respect to blood cancers where chronic conditions such as myeloproliferative neoplasms are due to mutations acquired in a haematopoietic stem cell (HSC), which maintains the normal hierarchy to neoplastic haematopoiesis. In contrast, acute leukaemia transformation of such blood neoplasms appears to derive not only from HSCs but also from committed progenitors that cannot differentiate. This review will focus on putative novel therapy targets represented by markers described to define cancer stem/initiating cells in malignant gliomas, which have been called ‘leukaemia of the brain’, given their rapid migration and evolution. Parallels are drawn with other cancers, especially haematopoietic, given the similar rampant proliferation and treatment resistance of glioblastoma multiforme and secondary acute leukaemias. Genes associated with the malignant conditions and especially expressed in glioma cancer stem cells are intensively searched. Although many such molecules might only coincidentally be expressed in cancer-initiating cells, some may function in the oncogenic process, and those would be the prime candidates for diagnostic and targeted therapy. For the latter, combination therapies are likely to be envisaged, given the robust and plastic signalling networks supporting malignant proliferation.

【 授权许可】

CC BY   
© 2013 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine

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