Targeting Heat Shock Proteins in Malignant Brain Tumors: From Basic Research to Clinical Trials
Babi A. Menlibayeva K. Bex T. Doskaliev A. Akshulakov S. Shevtsov M.
November 2022MDPI
Cancers
2022#14Issue 21
Heat shock proteins (HSPs) are conservative and ubiquitous proteins that are expressed both in prokaryotic and eukaryotic organisms and play an important role in cellular homeostasis, including the regulation of proteostasis, apoptosis, autophagy, maintenance of signal pathways, protection from various stresses (e.g., hypoxia, ionizing radiation, etc.). Therefore, HSPs are highly expressed in tumor cells, including malignant brain tumors, where they also associate with cancer cell invasion, metastasis, and resistance to radiochemotherapy. In the current review, we aimed to assess the diagnostic and prognostic values of HSPs expression in CNS malignancies as well as the novel treatment approaches to modulate the chaperone levels through the application of inhibitors (as monotherapy or in combination with other treatment modalities). Indeed, for several proteins (i.e., HSP10, HSPB1, DNAJC10, HSPA7, HSP90), a direct correlation between the protein level expression and poor overall survival prognosis for patients was demonstrated that provides a possibility to employ them as prognostic markers in neuro-oncology. Although small molecular inhibitors for HSPs, particularly for HSP27, HSP70, and HSP90 families, were studied in various solid and hematological malignancies demonstrating therapeutic potential, still their potential was not yet fully explored in CNS tumors. Some newly synthesized agents (e.g., HSP40/DNAJ inhibitors) have not yet been evaluated in GBM. Nevertheless, reported preclinical studies provide evidence and rationale for the application of HSPs inhibitors for targeting brain tumors.
brain tumors , glioblastoma , heat shock proteins , Hsp27 , Hsp40 , Hsp70 , Hsp90 , inhibitors , prognostic marker , small HSPs
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National Centre for Neurosurgery, Turan Ave., 34/1, Astana, 010000, Kazakhstan
Personalized Medicine Centre, Almazov National Medical Research Centre, 2 Akkuratova Str, Saint Petersburg, 197341, Russian Federation
Laboratory of Biomedical Nanotechnologies, Institute of Cytology of the Russian Academy of Sciences, Saint Petersburg, 194064, Russian Federation
Department of Radiation Oncology, Klinikum Rechts der Isar, Technical University of Munich, Munich, 81675, Germany
National Centre for Neurosurgery
Personalized Medicine Centre
Laboratory of Biomedical Nanotechnologies
Department of Radiation Oncology
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