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Targeting MELK in tumor cells and tumor microenvironment: from function and mechanism to therapeutic application
Pengfei Su1,2, Qiliang Lu1, Yuanyu Wang1
1Department of General Surgery, Cancer Center, Division of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310000, People's Republic of China.
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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