Brain tumour stem cells: possibilities of new therapeutic strategies

Abstract

Cancers are composed of heterogeneous cell populations, including highly proliferative immature precursors and differentiated cells, which may belong to different lineages. Recent advances in stem cell research have demonstrated the existence of tumour-initiating, cancer stem cells (CSCs) in non-solid and solid tumours. These cells are defined as CSCs because they show functional properties that resemble those of their normal counterpart to a significant extent. This concept applies to CSCs from brain tumours and, particularly, to glioblastoma stem-like cells, which self-renew under clonal conditions and differentiate into neuron- and glia-like cells, and into aberrant cells, with mixed neuronal/astroglia phenotypes. Notably, across serial transplantation into immunodeficient mice, glioblastoma stem-like cells are able to form secondary tumours which are a phenocopy of the human disease. A significant effort is underway to identify both CSC-specific markers and the molecular mechanism that underpin the tumorigenic potential of these cells, for this will have a critical impact on the understanding of the origin of malignant brain tumour and the discovery of new and more specific therapeutic approaches. Lately, the authors have shown that some of the bone morphogenetic proteins can reduce the tumorigenic ability of CSCs in GBMs. This suggests that mechanisms regulating the physiology of normal brain stem cells may be still in place in their cancerous siblings and that this may lead to the development of cures that selectively target the population CSCs found in the patients' tumour mass.

Emerging strategies for the identification and targeting of cancer stem cells

“…Additional challenges are presented by such factors as limited number of CSCs in tumor tissues, technical difficulties in keeping CSCs in any culture, and their unusually strong drug resistance. Generally speaking, with the growing evidence that CSCs exist in a wide array of tumors [1][2][3][9][10][11][12][13][14], studies of the hematopoietic origin and some solid tumors have provided proofs that cancers originate from CSCs. Therefore, cancer researchers all over the world now need to focus on exploring and developing methods to study the mechanisms that regulate the survival, self-renewal, and differentiation of normal and transformed stem cells.…”

Distinct pools of cancer stem-like cells coexist within human glioblastomas and display different tumorigenicity and independent genomic evolution

“…Oncogene (2009Oncogene ( ) 28, 1807Oncogene ( -1811doi:10.1038/onc.2009published online 16 March 2009 Keywords: brain tumours; cancer stem-like cells; tumorigenicity Glioblastomas (GBMs) are highly invasive, malignant brain tumours, whose prognosis remains dismal, despite aggressive surgery, radiotherapy and chemotherapy (Trent et al, 2002). The concept that a critical event in transformation might be the acquisition of an aberrant stem-like state (Reya et al, 2001) by a subset of cancer cells was recently extended to GBMs (Vescovi et al, 2006;Piccirillo and Vescovi, 2007).…”

Knockdown of Checkpoint Kinase 1 Is Associated with the Increased Radiosensitivity of Glioblastoma Stem-Like Cells

“…However, it has failed to show satisfactory efficacy in clinical practice (Narayana et al 2012). Potential reason for the inefficacy is the occurence of radioresistance in glioblastoma stem-like cells (Piccirillo and Vescovi 2007;Xie and Chin. 2008).…”