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脊索瘤中肿瘤坏死因子-α长期诱导的表皮生长因子受体酪氨酸激酶抑制剂耐药性分析

Analysis of long-term TNF-alpha induced EGFR tyrosine kinase inhibitor resistance in chordoma.

作者信息

Tang HaoShuai, Zhu QingRun, Fan JinHong, Li XinAo, Yan ZhenYe, Wang Feng, Wang HaiFeng, Wang DaChuan

机构信息

Department of Orthopaedics, The Second Qilu Hospital of Shandong University No. 247 Beiyuan Street Tianqiao District Jinan 250033 China

出版信息

RSC Med Chem. 2025 Sep 9. doi: 10.1039/d5md00258c.

Abstract

Chordoma is a special malignant tumor that lacks effective therapeutic targets, which can lead to incomplete treatment and metastasis. Inflammation plays an important role in chordoma progression and malignant phenotype. Inflammatory factors such as NF-kappaB and STAT3 are continuously activated in many tumors and contribute to the malignant phenotype of tumors and are potential therapeutic targets. This study suggest TNF-alpha and NF-kappaB signaling pathways were consistently activated in chordomas. Long-term TNF-alpha treatment induces chordoma resistance to EGFR family inhibitors. The underlying mechanism is realized by the key molecules HS3ST3A and HS3ST3B1. These two enzymes are potential targets for chordoma treatment, as well as for combination drugs treatment. It should be emphasized that the above analysis lacks experimental verification.

摘要

脊索瘤是一种缺乏有效治疗靶点的特殊恶性肿瘤,可导致治疗不彻底和转移。炎症在脊索瘤进展和恶性表型中起重要作用。诸如核因子κB和信号转导与转录激活因子3等炎症因子在许多肿瘤中持续激活,促成肿瘤的恶性表型,是潜在的治疗靶点。本研究表明,肿瘤坏死因子-α和核因子κB信号通路在脊索瘤中持续激活。长期肿瘤坏死因子-α治疗可诱导脊索瘤对表皮生长因子受体家族抑制剂产生耐药性。其潜在机制是通过关键分子硫酸乙酰肝素3-O-磺基转移酶3A和硫酸乙酰肝素3-O-磺基转移酶3B1实现的。这两种酶是脊索瘤治疗以及联合药物治疗的潜在靶点。应当强调的是,上述分析缺乏实验验证。

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