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An Update on Glioblastoma Biology, Genetics, and Current Therapies: Novel Inhibitors of the G Protein-Coupled Receptor CCR5
- Source :
- International Journal of Molecular Sciences, Vol 22, Iss 4464, p 4464 (2021), International Journal of Molecular Sciences
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- The mechanisms governing therapeutic resistance of the most aggressive and lethal primary brain tumor in adults, glioblastoma, have increasingly focused on tumor stem cells. These cells, protected by the periarteriolar hypoxic GSC niche, contribute to the poor efficacy of standard of care treatment of glioblastoma. Integrated proteogenomic and metabolomic analyses of glioblastoma tissues and single cells have revealed insights into the complex heterogeneity of glioblastoma and stromal cells, comprising its tumor microenvironment (TME). An additional factor, which isdriving poor therapy response is the distinct genetic drivers in each patient’s tumor, providing the rationale for a more individualized or personalized approach to treatment. We recently reported that the G protein-coupled receptor CCR5, which contributes to stem cell expansion in other cancers, is overexpressed in glioblastoma cells. Overexpression of the CCR5 ligand CCL5 (RANTES) in glioblastoma completes a potential autocrine activation loop to promote tumor proliferation and invasion. CCL5 was not expressed in glioblastoma stem cells, suggesting a need for paracrine activation of CCR5 signaling by the stromal cells. TME-associated immune cells, such as resident microglia, infiltrating macrophages, T cells, and mesenchymal stem cells, possibly release CCR5 ligands, providing heterologous signaling between stromal and glioblastoma stem cells. Herein, we review current therapies for glioblastoma, the role of CCR5 in other cancers, and the potential role for CCR5 inhibitors in the treatment of glioblastoma.
- Subjects :
- 0301 basic medicine
Stromal cell
Receptors, CCR5
QH301-705.5
Antineoplastic Agents
Review
Biology
Catalysis
CCL5
Inorganic Chemistry
03 medical and health sciences
Paracrine signalling
0302 clinical medicine
intertumoral heterogeneity
medicine
Animals
Humans
Molecular Targeted Therapy
Physical and Theoretical Chemistry
perivascular niche
Biology (General)
Autocrine signalling
Molecular Biology
glioblastoma therapy
neoplasms
QD1-999
Spectroscopy
Tumor microenvironment
Microglia
glioblastoma stem cells
Brain Neoplasms
Organic Chemistry
Mesenchymal stem cell
glioblastoma
General Medicine
cytokines
Computer Science Applications
nervous system diseases
Chemistry
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
Cancer research
Stem cell
CCR5
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 16616596 and 14220067
- Volume :
- 22
- Issue :
- 4464
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....dbed0fc8cb30195ddf6c7f9465e88361