Abstract
Patients with glioblastoma (GB), a highly aggressive brain tumor, have a median survival of 14.6 months following neurosurgical resection and adjuvant chemoradiotherapy. Quiescent GB cancer stem cells (CSCs) invariably cause local recurrence. These GB CSCs can be identified by embryonic stem cell markers, express components of the renin-angiotensin system (RAS) and are associated with circulating CSCs. Despite the presence of circulating CSCs, GB patients rarely develop distant metastasis outside the central nervous system. This paper reviews the current literature on GB growth inhibition in relation to CSCs, circulating CSCs, the RAS and the novel therapeutic approach by repurposing drugs that target the RAS to improve overall symptom-free survival and maintain quality of life.
Highlights
Human astrocytic tumors are the most common primary intra-axial brain tumors
Cancer stem cells (CSCs) in human brain tumors were initially discovered by the identification of cells expressing the cell surface marker CD133, a cell surface pentaspan transmembrane glycoprotein located in plasma membrane protrusions [12]
We demonstrated the expression of components of the renin-angiotensin system (RAS): pro-renin receptor (PRR), angiotensin-converting enzyme (ACE), ATII receptor 1 (ATIIR1) and ATII receptor 2 (ATIIR2) by cancer stem cells (CSCs) in different cancer types including head and neck cutaneous squamous cell carcinoma (SCC) [69], oral cavity SCC (OCSCC) affecting the
Summary
Human astrocytic tumors are the most common primary intra-axial brain tumors. Under the World Health Organization (WHO) classification of central nervous system tumors, grade I astrocytomas include the more well-circumscribed pilocytic astrocytomas, in contrast to grade II to IV diffuse astrocytomas [1]. Methylation of the O6 -methylguanine-DNA methyltransferase (MGMT) promoter is associated with better response to temozolomide and prolonged survival. The recent revision of the WHO classification of central nervous system tumors incorporates molecular parameters: a paradigm shift that provides dynamic phenotype and genotype classifications that impacts on prognosis and outcomes. Known intrinsic factors affecting the prognosis of GB include isocitrate dehydrogenase (IDH) mutation and methylation of the MGMT gene. GBs are divided into IDH-wildtype (90% of cases) and IDH-mutant tumors [1]. IDH mutants with methylation fingerprints [6] are associated with a better survival rate due to the accumulation of 2-hydroxyglutarate, secondary to loss of normal enzymatic function [7], increasing the sensitivity of the tumors to selective chemoradiotherapy [8]. GB cell biology, fueled intense research to find novel therapeutic targets, at the genomic and molecular levels
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