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1 型胰岛素样生长因子受体与儿科高级别胶质瘤的不良预后和细胞放射抵抗有关。

Type 1 IGF receptor associates with adverse outcome and cellular radioresistance in paediatric high-grade glioma.

机构信息

Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.

Nuffield Department of Clinical Neurosciences, University of Oxford, Level 6, West Wing, John Radcliffe Hospital, Oxford, OX3 9DU, UK.

出版信息

Br J Cancer. 2020 Mar;122(5):624-629. doi: 10.1038/s41416-019-0677-1. Epub 2019 Dec 20.

DOI:10.1038/s41416-019-0677-1
PMID:31857716
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7054265/
Abstract

High-grade glioma (HGG) is highly resistant to therapy, prompting us to investigate the contribution of insulin-like growth factor receptor (IGF-1R), linked with radioresistance in other cancers. IGF-1R immunohistochemistry in 305 adult HGG (aHGG) and 103 paediatric/young adult HGG (pHGG) cases revealed significant association with adverse survival in pHGG, with median survival of 13.5 vs 29 months for pHGGs with moderate/strong vs negative/weak IGF-1R (p = 0.011). Secondly, we tested IGF-1R inhibitor BMS-754807 in HGG cells, finding minimal radiosensitisation of 2/3 aHGG cell lines (dose enhancement ratios DERs < 1.60 at 2-8 Gy), and greater radiosensitisation of 2/2 pHGG cell lines (DERs ≤ 4.16). BMS-754807 did not influence radiation-induced apoptosis but perturbed the DNA damage response with altered induction/resolution of γH2AX, 53BP1 and RAD51 foci. These data indicate that IGF-1R promotes radioresistance in pHGG, potentially contributing to the association of IGF-1R with adverse outcome and suggesting IGF-1R as a candidate treatment target in pHGG.

摘要

高级别胶质瘤（HGG）对治疗具有高度抗性，促使我们研究胰岛素样生长因子受体（IGF-1R）的作用，因为它与其他癌症的放射抗性有关。在 305 例成人 HGG（aHGG）和 103 例小儿/青年成人 HGG（pHGG）病例中进行 IGF-1R 免疫组织化学检测显示，IGF-1R 与 pHGG 的不良生存结果显著相关，中度/强 IGF-1R 表达的 pHGG 的中位生存期为 13.5 个月，而阴性/弱 IGF-1R 表达的 pHGG 的中位生存期为 29 个月（p = 0.011）。其次，我们在 HGG 细胞中测试了 IGF-1R 抑制剂 BMS-754807，发现 2/3 的 aHGG 细胞系的放射增敏作用最小（2-8Gy 时剂量增强比 DER ＜1.60），而 2/2 的 pHGG 细胞系的放射增敏作用更大（DER ≤4.16）。BMS-754807 不影响辐射诱导的细胞凋亡，但通过改变 γH2AX、53BP1 和 RAD51 焦点的诱导/解决来扰乱 DNA 损伤反应。这些数据表明，IGF-1R 促进了 pHGG 的放射抗性，可能与 IGF-1R 与不良预后的关联有关，并提示 IGF-1R 是 pHGG 的候选治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/873b/7054265/7d309ab0fcfc/41416_2019_677_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/873b/7054265/c3d26b6e5312/41416_2019_677_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/873b/7054265/7d309ab0fcfc/41416_2019_677_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/873b/7054265/c3d26b6e5312/41416_2019_677_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/873b/7054265/7d309ab0fcfc/41416_2019_677_Fig2_HTML.jpg

相似文献

[1]
Type 1 IGF receptor associates with adverse outcome and cellular radioresistance in paediatric high-grade glioma.

Br J Cancer. 2019-12-20

[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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Mol Cancer Ther. 2014-12-19

[8]
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Oncogene. 2014-11-6

[9]
IGF-1R depletion sensitizes colon cancer cell lines to radiotherapy.

Cancer Biomark. 2021

[10]
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Cancer Med. 2015-1

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[1]
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J Gastrointest Cancer. 2025-1-24

[2]
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Front Immunol. 2024

[3]
Targeting IGF2 to reprogram the tumor microenvironment for enhanced viro-immunotherapy.

Neuro Oncol. 2024-9-5

[4]
Prognosis and therapeutic significance of IGF-1R-related signaling pathway gene signature in glioma.

Front Cell Dev Biol. 2024-4-11

[5]
A Systematic Review of the Metabolism of High-Grade Gliomas: Current Targeted Therapies and Future Perspectives.

Int J Mol Sci. 2024-1-5

[6]
GALNT2, an O-glycosylating enzyme, is a critical regulator of radioresistance of non-small cell lung cancer: evidence from an integrated multi-omics analysis.

Cell Biol Toxicol. 2023-12

[7]
Targeting the IGF-Axis in Cultured Pediatric High-Grade Glioma Cells Inhibits Cell Cycle Progression and Survival.

Pharmaceuticals (Basel). 2023-2-14

[8]
Prognostic RNA-editing signature predicts immune functions and therapy responses in gliomas.

Front Genet. 2023-2-8

[9]
Glioma stem cell signature predicts the prognosis and the response to tumor treating fields treatment.

CNS Neurosci Ther. 2022-12

[10]
Dual IGF1R/IR inhibitors in combination with GD2-CAR T-cells display a potent anti-tumor activity in diffuse midline glioma H3K27M-mutant.

Neuro Oncol. 2022-7-1

本文引用的文献

[1]
Newly Diagnosed Glioblastoma: A Review on Clinical Management.

Oncology (Williston Park). 2019-3-13

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