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Review
. 2023 Dec 19;20(2):24.
doi: 10.3892/br.2023.1712. eCollection 2024 Feb.

Regulation of cancer stem cells and immunotherapy of glioblastoma (Review)

Аleksandra Kosianova  1 , Oleg Pak  1 , Igor Bryukhovetskiy  1
Affiliations
Review

Regulation of cancer stem cells and immunotherapy of glioblastoma (Review)

Аleksandra Kosianova et al. Biomed Rep. .

Abstract

Glioblastoma (GB) is one of the most adverse diagnoses in oncology. Complex current treatment results in a median survival of 15 months. Resistance to treatment is associated with the presence of cancer stem cells (CSCs). The present review aimed to analyze the mechanisms of CSC plasticity, showing the particular role of β-catenin in regulating vital functions of CSCs, and to describe the molecular mechanisms of Wnt-independent increase of β-catenin levels, which is influenced by the local microenvironment of CSCs. The present review also analyzed the reasons for the low effectiveness of using medication in the regulation of CSCs, and proposed the development of immunotherapy scenarios with tumor cell vaccines, containing heterogenous cancer cells able of producing a multidirectional antineoplastic immune response. Additionally, the possibility of managing lymphopenia by transplanting hematopoietic stem cells from a healthy sibling and using clofazimine or other repurposed drugs that reduce β-catenin concentration in CSCs was discussed in the present study.

Keywords: cancer stem cells; glioblastoma; immunotherapy; microenvironment; targeted therapy; β-catenin.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Repurposed drugs targeting the Wnt/β-catenin signaling pathway: (A) Aspirin (acetylsalicylic acid), (B) celecoxib, (С) indomethacin, (D) sulindac, (Е) tigecycline, (F) niclosamide, (G) pyrvinium pamoate, (H) ivermectin and (I) clofazimine.
Figure 2
Figure 2
Association between the level of leukocytes (green color) after multiple cycles of chemotherapy and aggressiveness of GB. The red color indicates cancer stem cells of GB. The yellow color indicates the differentiated cells of GB. GB, glioblastoma; CRT, chemoradiotherapy; TMZ, temozolomide.
Figure 3
Figure 3
Scheme of the relationship between β-catenin activity and immunotherapy. LRP, low-density lipoprotein receptor-related protein; LPS, lipopolysaccharide.
Figure 4
Figure 4
Hypothetical scheme for personalized therapy of glioblastoma using inhibitors of the Wnt/β-catenin signaling pathway and immunotherapy.
See this image and copyright information in PMC

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