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Heterogeneity and individualized treatment of microenvironment in glioblastoma (Review).

ABSTRACT: The heterogeneity of glioblastoma can suppress immune cell function and lead to immune evasion, which presents a challenge in developing effective molecular therapies for tumor cells. However, the study of tumor immune heterogeneity holds great potential for clinical immunotherapy. Liquid biopsy is a useful tool for accurately monitoring dynamic changes in tumor immune heterogeneity and the tumor microenvironment. This paper explores the heterogeneity of glioblastoma and the immune microenvironment, providing a therapeutic basis for individualized treatment. Using liquid biopsy technology as a new diagnostic method, innovative treatment strategies may be implemented for patients with glioblastoma to improve their outcomes.

SUBMITTER: Kang W

PROVIDER: S-EPMC10636722 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Heterogeneity and individualized treatment of microenvironment in glioblastoma (Review).

Kang Wei W Mo Zhixiao Z Li Wenshan W Ma Haifeng H Zhang Qiang Q

Oncology reports 20231027 6

The heterogeneity of glioblastoma can suppress immune cell function and lead to immune evasion, which presents a challenge in developing effective molecular therapies for tumor cells. However, the study of tumor immune heterogeneity holds great potential for clinical immunotherapy. Liquid biopsy is a useful tool for accurately monitoring dynamic changes in tumor immune heterogeneity and the tumor microenvironment. This paper explores the heterogeneity of glioblastoma and the immune microenvironm ...[more]

PMID: 37888767

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Project description:BackgroundA major barrier to effective treatment of glioblastoma (GBM) is the large intertumoral heterogeneity at the genetic and cellular level. In early phase clinical trials, patient heterogeneity in response to therapy is commonly observed; however, how tumor heterogeneity is reflected in individual drug sensitivities in the treatment-naïve glioblastoma stem cells (GSC) is unclear.MethodsWe cultured 12 patient-derived primary GBMs as tumorspheres and validated tumor stem cell properties by functional assays. Using automated high-throughput screening (HTS), we evaluated sensitivity to 461 anticancer drugs in a collection covering most FDA-approved anticancer drugs and investigational compounds with a broad range of molecular targets. Statistical analyses were performed using one-way ANOVA and Spearman correlation.ResultsAlthough tumor stem cell properties were confirmed in GSC cultures, their in vitro and in vivo morphology and behavior displayed considerable tumor-to-tumor variability. Drug screening revealed significant differences in the sensitivity to anticancer drugs (p < 0.0001). The patient-specific vulnerabilities to anticancer drugs displayed a heterogeneous pattern. They represented a variety of mechanistic drug classes, including apoptotic modulators, conventional chemotherapies, and inhibitors of histone deacetylases, heat shock proteins, proteasomes and different kinases. However, the individual GSC cultures displayed high biological consistency in drug sensitivity patterns within a class of drugs. An independent laboratory confirmed individual drug responses.ConclusionsThis study demonstrates that patient-derived and treatment-naïve GSC cultures maintain patient-specific traits and display intertumoral heterogeneity in drug sensitivity to anticancer drugs. The heterogeneity in patient-specific drug responses highlights the difficulty in applying targeted treatment strategies at the population level to GBM patients. However, HTS can be applied to uncover patient-specific drug sensitivities for functional precision medicine.

Dataset Information

Heterogeneity and individualized treatment of microenvironment in glioblastoma (Review).

Publications

Heterogeneity and individualized treatment of microenvironment in glioblastoma (Review).

Similar Datasets

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