Maternal Embryonic Leucine Zipper Kinase (MELK) in Cancer: Biological Functions, Therapeutic Potential, and Controversies

The Maternal Embryonic Leucine Zipper Kinase (<i>MELK</i>) gene is a member of the Snf1/AMPK serine/threonine kinase family. <i>MELK</i> has recently attracted considerable interest in cancer biology due to its aberrant overexpression in various malignancies, including glioma, breast, lung, colorectal, gastric, and hematological cancers. It has been shown that higher <i>MELK</i> levels are often correlated with unfavorable prognosis, aggressive tumor manifestations, resistance to treatment, and stem-like tumor morphologies. In this review we aim to summarize the current understanding of <i>MELK</i> biology, including its functions in cell cycle regulation, apoptosis, oncogenic signaling pathways, and tumor stemness. We also discuss the therapeutic potential, limitations, and controversy of <i>MELK</i> inhibitors, and implications in cancer diagnosis and treatment. <i>MELK</i> may not be a universal driver oncogene; nonetheless, it is consistently linked to aggressive disease, underscoring its potential as a prognostic biomarker and a candidate for therapeutic co-targeting in combination treatments.