Cancer stem cells in meningiomas: novel insights and therapeutic implications

Abstract

Meningiomas (MGs), which arise from meningothelial cells of the dura mater, represent a significant proportion of primary tumours of the central nervous system (CNS). Despite advances in treatment, the management of malignant meningioma (MMG) remains challenging due to diagnostic, surgical, and resection limitations. Cancer stem cells (CSCs), a subpopulation within tumours capable of self-renewal and differentiation, are highlighted as key markers of tumour growth, metastasis, and treatment resistance. Identifying additional CSC-related markers enhances the precision of malignancy evaluations, enabling advancements in personalised medicine. The review discusses key CSC biomarkers that are associated with high levels of expression, aggressive tumour behaviour, and poor outcomes. Recent molecular research has identified CSC-related biomarkers, including Oct-4, Sox2, NANOG, and CD133, which help maintain cellular renewal, proliferation, and drug resistance in MGs. This study highlights new therapeutic strategies that could improve patient prognosis with more durable tumour regression. The use of combination therapies, such as hydroxyurea alongside diltiazem, suggests more efficient and effective MG management compared to monotherapy. Signalling pathways such as NOTCH and hedgehog also offer additional avenues for therapeutic development. CRISPR/Cas9 technology has also been employed to create meningioma models, uncovering pathways related to cell growth and proliferation. Since the efficacy of traditional therapies is limited in most cases due to resistance mechanisms in CSCs, further studies on the biology of CSCs are warranted to develop therapeutic interventions that are likely to be effective in MG. Consequently, improved diagnostic approaches may lead to personalised treatment plans tailored to the specific needs of each patient.

Keywords: Meningioma; Meningioma stem cells; Neuro-genetics; Neuro-oncology.

Fig. 1

An overview of the World Health Organisation grades of meningiomas (Created with Biorender.com).WHO: World Health Organisation

Fig. 2

A comprehensive review of the genetics and pathogenesis of meningiomas (Created with Biorender.com).CSF, cerebrospinal fluid; NF2, neurofibromatosis 2; KLF4, Krüppel-like factor 4; TRAF7, tumour necrosis factor receptor-associated factor 7; SMO, smoothened; AKT1, v-Akt murine thymoma viral oncogene homolog 1; VHL, Von Hippel–Lindau; MEN1, multiple endocrine neoplasia type 1

Fig. 3

Overview of Cancer Stem Cell characteristics and potential drug targets (Created with Biorender.com).CSCs: cancer stem cells, DNA: deoxyribonucleic acid, ABC: adenosine triphosphate-binding cassette, MDR: multidrug resistance, JAK: Janus kinase, STAT: signal transducer and activator of transcription, MAP-kinase: mitogen-activated protein kinase, NOTCH: neurogenic locus notch homolog protein, ERK: extracellular-signal-regulated kinase, PI3K: phosphatidylinositol-3 kinase, TGF-β: transforming growth factor beta, ZEB1: zinc finger E-box binding homeobox-1, NF-kB: nuclear factor-kappa B, WNT: wingless-related integration site

Fig. 4

Correlation between cancer stem cell renewal, resistance, and recurrence (created with Biorender.com). IL-6: interleukin-6, Nf-kB: nuclear factor-kappa B, JAK: Janus kinase, STAT: signal transducer and activator of transcription, TNF-alpha: tumour necrosis factor-alpha, WNT: wingless-related integration site, SHH: sonic hedgehog, NOTCH: neurogenic locus notch homolog protein, IFN-γ: interferon gamma, CXCL: CXC chemokine ligand, CTNNB: catenin beta, CCND: Cyclin D, ENC: ectodermal-neural cortex 1, BMP: bone morphogenic protein, RA: retinoic acid, GSTPE: glutathione s-transferase P, Oct-4: octamer-binding transcription factor 4, Sox2: sex-determining region Y-box 2