It's all downstream from here: RTK/Raf/MEK/ERK pathway resistance mechanisms in glioblastoma.

IF 3.2 2区医学 Q2 CLINICAL NEUROLOGY

Journal of Neuro-Oncology Pub Date : 2025-01-16 DOI:10.1007/s11060-024-04930-w

Rebeca Yakubov, Ramneet Kaloti, Phooja Persaud, Anna McCracken, Gelareh Zadeh, Severa Bunda

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引用次数: 0

Abstract

Background: The receptor tyrosine kinase (RTK)/Ras/Raf/MEK/ERK signaling pathway is one of the most tumorigenic pathways in cancer, with its hyperactivation strongly linked to the aggressive nature of glioblastoma (GBM). Although extensive research has focused on developing therapeutics targeting this pathway, clinical success remains elusive due to the emergence of resistance mechanisms.

Objective: This review investigates how inhibition of the RTK/Ras/Raf/MEK/ERK pathway alters transcription factors, contributing to acquired resistance mechanisms in GBM. It also highlights the critical role of transcription factor dysregulation in therapeutic resistance.

Methods & results: Findings from key studies on the RTK/Ras/Raf/MEK/ERK pathway in GBM were synthesized to explore the role of transcription factor dysregulation in resistance to targeted therapies, radiation, and chemotherapy. The review highlights that transcription factors undergo significant dysregulation following RTK/Ras/Raf/MEK/ERK pathway inhibition, contributing to therapeutic resistance.

Conclusion: Transcription factors are promising targets for overcoming treatment resistance in GBM, with cotreatment strategies combining RTK/Ras/Raf/MEK/ERK pathway inhibitors and transcription factor-targeted therapies presenting a novel approach. Despite the challenges of targeting complex structures and interactions, advancements in drug development and precision technologies hold great potential. Continued research is essential to refine these strategies and improve outcomes for GBM and other aggressive cancers.

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这都是从这里开始的：胶质母细胞瘤中的RTK/Raf/MEK/ERK通路耐药机制。

背景：受体酪氨酸激酶(RTK)/Ras/Raf/MEK/ERK信号通路是肿瘤中最具致瘤性的信号通路之一，其过度激活与胶质母细胞瘤（GBM）的侵袭性密切相关。尽管广泛的研究集中于开发针对这一途径的治疗方法，但由于耐药机制的出现，临床成功仍然难以捉摸。目的：本文综述了抑制RTK/Ras/Raf/MEK/ERK通路如何改变转录因子，从而参与GBM获得性耐药机制。它还强调了转录因子失调在治疗耐药中的关键作用。方法与结果：综合GBM中RTK/Ras/Raf/MEK/ERK通路的关键研究结果，探讨转录因子失调在靶向治疗、放疗和化疗耐药中的作用。该综述强调，转录因子在RTK/Ras/Raf/MEK/ERK通路抑制后发生显著的失调，从而导致治疗耐药。结论：转录因子是克服GBM治疗耐药的有希望的靶点，RTK/Ras/Raf/MEK/ERK通路抑制剂与转录因子靶向治疗相结合的共治疗策略提供了一种新的途径。尽管针对复杂结构和相互作用的挑战，药物开发和精密技术的进步具有巨大的潜力。持续的研究对于完善这些策略和改善GBM和其他侵袭性癌症的预后至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Neuro-Oncology 医学-临床神经学

CiteScore

6.60

自引率

7.70%

发文量

277

审稿时长

3.3 months

期刊介绍： The Journal of Neuro-Oncology is a multi-disciplinary journal encompassing basic, applied, and clinical investigations in all research areas as they relate to cancer and the central nervous system. It provides a single forum for communication among neurologists, neurosurgeons, radiotherapists, medical oncologists, neuropathologists, neurodiagnosticians, and laboratory-based oncologists conducting relevant research. The Journal of Neuro-Oncology does not seek to isolate the field, but rather to focus the efforts of many disciplines in one publication through a format which pulls together these diverse interests. More than any other field of oncology, cancer of the central nervous system requires multi-disciplinary approaches. To alleviate having to scan dozens of journals of cell biology, pathology, laboratory and clinical endeavours, JNO is a periodical in which current, high-quality, relevant research in all aspects of neuro-oncology may be found.