Midkine (MDK) in cancer and drug resistance: from inflammation to therapy

Abstract Midkine (MDK) is a heparin-binding growth factor implicated in the pathogenesis of various diseases, including cancer, chronic inflammation, and multidrug resistance (MDR). While its expression is minimal in adult tissues, it becomes markedly elevated during embryogenesis and in response to...

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Main Authors: Berna Yıldırım, Kudret Kulak, Ayhan Bilir
Format: Article
Language:English
Published: Springer 2025-06-01
Series:Discover Oncology
Subjects:
Online Access:https://doi.org/10.1007/s12672-025-02941-1
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author Berna Yıldırım
Kudret Kulak
Ayhan Bilir
author_facet Berna Yıldırım
Kudret Kulak
Ayhan Bilir
author_sort Berna Yıldırım
collection DOAJ
description Abstract Midkine (MDK) is a heparin-binding growth factor implicated in the pathogenesis of various diseases, including cancer, chronic inflammation, and multidrug resistance (MDR). While its expression is minimal in adult tissues, it becomes markedly elevated during embryogenesis and in response to injury, infection, or hypoxia. MDK modulates inflammatory responses by recruiting immune cells and enhancing proinflammatory cytokine production. In oncogenesis, it promotes tumor proliferation, angiogenesis, epithelial-to-mesenchymal transition (EMT), and therapeutic resistance. Elevated MDK levels are frequently associated with aggressive tumor behavior and poor clinical outcomes. This review synthesizes current knowledge on MDK’s expression profiles, molecular mechanisms, and functional roles across pathological conditions. It also discusses MDK’s emerging value as a diagnostic and prognostic biomarker, and highlights recent advances in therapeutic strategies including small molecule inhibitors, RNA-based approaches, and receptor-blocking peptides. Overall, MDK represents a promising target for future personalized therapies, although further preclinical and clinical validation is warranted to confirm its translational potential.
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spelling doaj-art-b512f80a8a5443a386fd8ac60b642d162025-08-20T02:07:45ZengSpringerDiscover Oncology2730-60112025-06-0116111910.1007/s12672-025-02941-1Midkine (MDK) in cancer and drug resistance: from inflammation to therapyBerna Yıldırım0Kudret Kulak1Ayhan Bilir2Department of Histology and Embryology, Faculty of Medicine, İstanbul Atlas UniversityDepartment of Pediatrics, Faculty of Medicine, İstanbul Atlas UniversityDepartment of Histology and Embryology, Faculty of Medicine, İstanbul Atlas UniversityAbstract Midkine (MDK) is a heparin-binding growth factor implicated in the pathogenesis of various diseases, including cancer, chronic inflammation, and multidrug resistance (MDR). While its expression is minimal in adult tissues, it becomes markedly elevated during embryogenesis and in response to injury, infection, or hypoxia. MDK modulates inflammatory responses by recruiting immune cells and enhancing proinflammatory cytokine production. In oncogenesis, it promotes tumor proliferation, angiogenesis, epithelial-to-mesenchymal transition (EMT), and therapeutic resistance. Elevated MDK levels are frequently associated with aggressive tumor behavior and poor clinical outcomes. This review synthesizes current knowledge on MDK’s expression profiles, molecular mechanisms, and functional roles across pathological conditions. It also discusses MDK’s emerging value as a diagnostic and prognostic biomarker, and highlights recent advances in therapeutic strategies including small molecule inhibitors, RNA-based approaches, and receptor-blocking peptides. Overall, MDK represents a promising target for future personalized therapies, although further preclinical and clinical validation is warranted to confirm its translational potential.https://doi.org/10.1007/s12672-025-02941-1Midkine (MDK)Multidrug resistanceInflammatory diseasesCancer
spellingShingle Berna Yıldırım
Kudret Kulak
Ayhan Bilir
Midkine (MDK) in cancer and drug resistance: from inflammation to therapy
Discover Oncology
Midkine (MDK)
Multidrug resistance
Inflammatory diseases
Cancer
title Midkine (MDK) in cancer and drug resistance: from inflammation to therapy
title_full Midkine (MDK) in cancer and drug resistance: from inflammation to therapy
title_fullStr Midkine (MDK) in cancer and drug resistance: from inflammation to therapy
title_full_unstemmed Midkine (MDK) in cancer and drug resistance: from inflammation to therapy
title_short Midkine (MDK) in cancer and drug resistance: from inflammation to therapy
title_sort midkine mdk in cancer and drug resistance from inflammation to therapy
topic Midkine (MDK)
Multidrug resistance
Inflammatory diseases
Cancer
url https://doi.org/10.1007/s12672-025-02941-1
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