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.
Background: The study aimed to analyze the 5-year survival of adult patients with glial tumors and to define characteristics that are associated with the disease outcomes in Kazakhstan. Methods: Medical records of patients that were surgically treated at the National Center for Neurosurgery during the 5-year period from 2016 to 2020 were collected retrospectively. Patients with a histologically confirmed diagnosis of diffuse astrocytic or oligodendroglial tumor type were included and their survival was assessed with life tables, Kaplan–Meier plot, and Cox regression using STATA 16 statistical software. Results: Almost half of the patients had glioblastoma. The 5-year survival rate of the whole sample was 45.93%. Among Grade 4 patients, 15.6% survived the 5-year mark. Differences in survival between grades 1–3 were not significant. Grade 1 patients demonstrated worse survival rates compared to Grade 2 patients (69% vs. 74%). Worse survival rates were observed among patients of Russian ethnicity and in rural residents. Conclusions: The study described the unusual patterns in survival rates of glial tumor patients in Kazakhstan, pointing to the need for reassessment of diagnostic accuracy and resulting treatment of glial patients in Kazakhstan, and the need to introduce molecular and genetic parameters in tumor type classification. Moreover, the observed difference in survival of different ethnic groups and residents of rural and urban areas should be further investigated and addressed by healthcare professionals.
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