Targeting MELK in tumor cells and tumor microenvironment: from function and mechanism to therapeutic application.

IF 2.8 3区医学 Q2 ONCOLOGY

Clinical & Translational Oncology Pub Date : 2025-03-01 Epub Date: 2024-08-26 DOI:10.1007/s12094-024-03664-5

Pengfei Su, Qiliang Lu, Yuanyu Wang, Yiping Mou, Weiwei Jin

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Abstract

Maternal embryonic leucine zipper kinase (MELK), a member of the adenosine monophosphate-activated protein kinase (AMPK) protein family, has been reported to be involved in the regulation of many cellular events. The aberrant expression of MELK is associated with tumorigenesis and malignant progression of various tumors. Moreover, MELK plays an essential role in the regulation of tumor microenvironment (TME), which affects the function of immune cells and the responsiveness to immunotherapy. Currently, small molecule inhibitors targeting MELK have been developed and evaluated in clinical trials. A comprehensive understanding of MELK may provide clues and confidence for subsequent basic research and scientific transformation. In this review, we provide a comprehensive overview of the structural features, molecular biological functions, and critical roles of MELK in tumors and TME, as well as the targeted agents under development for the treatment of tumors and discuss the perspective for MELK-targeted therapies for tumors.

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靶向肿瘤细胞和肿瘤微环境中的 MELK：从功能和机制到治疗应用。

母体胚胎亮氨酸拉链激酶（MELK）是单磷酸腺苷激活蛋白激酶（AMPK）蛋白家族的成员，据报道它参与了许多细胞事件的调控。MELK 的异常表达与各种肿瘤的发生和恶性进展有关。此外，MELK 在调控肿瘤微环境（TME）中发挥着重要作用，而肿瘤微环境会影响免疫细胞的功能和对免疫疗法的反应性。目前，针对 MELK 的小分子抑制剂已被开发出来，并在临床试验中进行了评估。全面了解 MELK 可为后续的基础研究和科学转化提供线索和信心。在这篇综述中，我们将全面概述MELK的结构特征、分子生物学功能、在肿瘤和TME中的关键作用，以及正在开发的用于治疗肿瘤的靶向药物，并探讨MELK靶向治疗肿瘤的前景。

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

Clinical & Translational Oncology 医学-肿瘤学

CiteScore

6.20

自引率

2.90%

发文量

240

审稿时长

1 months

期刊介绍： Clinical and Translational Oncology is an international journal devoted to fostering interaction between experimental and clinical oncology. It covers all aspects of research on cancer, from the more basic discoveries dealing with both cell and molecular biology of tumour cells, to the most advanced clinical assays of conventional and new drugs. In addition, the journal has a strong commitment to facilitating the transfer of knowledge from the basic laboratory to the clinical practice, with the publication of educational series devoted to closing the gap between molecular and clinical oncologists. Molecular biology of tumours, identification of new targets for cancer therapy, and new technologies for research and treatment of cancer are the major themes covered by the educational series. Full research articles on a broad spectrum of subjects, including the molecular and cellular bases of disease, aetiology, pathophysiology, pathology, epidemiology, clinical features, and the diagnosis, prognosis and treatment of cancer, will be considered for publication.