The role of MELK in cancer: mechanisms and therapeutic options
TL;DR
A comprehensive perspective on MELK is offered that stands out in the existing literature for its critical evaluation of context-dependent functions and therapeutic relevance and highlights key gaps that must be addressed to establish MELK as a reliable cancer biomarker and therapeutic target.
Abstract
Cells undergo tight regulation during the mitotic phase of the cell cycle, which produces genetically identical daughter cells and prevents the segregation of duplicate chromosomes. This regulatory network has identified maternal embryonic leucine zipper kinase (MELK) as a proliferation-associated regulator. MELK is highly expressed in actively dividing cells and is often overexpressed in multiple human cancers. Beyond its canonical role in mitotic regulation, MELK is implicated in numerous oncogenic processes, including transcriptional and epigenetic regulation, inflammation, epithelial-mesenchymal transition (EMT), DNA damage response (DDR), and treatment resistance. Even though pharmacological inhibition of MELK has shown encouraging anticancer effects in preclinical models, its biological requirement remains context-dependent and poorly understood. By integrating mechanistic insights with translational and clinical evidence, this review offers a comprehensive perspective on MELK that stands out in the existing literature for its critical evaluation of context-dependent functions and therapeutic relevance. We highlight key gaps that must be addressed to establish MELK as a reliable cancer biomarker and therapeutic target.