Human Melanoma Skin Cancer Models: A Step Towards Drug Testing & Target Therapy Publisher



Barghian Zarnaghi B^{1, 2} ; Barghian Zarnaghi E^{1, 2} ; Nilforoushzadeh MA² ; Roshanzamir N³ ; Amirkhani MA² ; Mollapour Sisakht M^{1, 4, 5} Show Affiliations
Source: Stem Cell Reviews and Reports Published:2025

Abstract

Melanoma is one of the most aggressive types of solid cancer, originating in melanocytes. Due to its complex and heterogeneous nature, it can respond very differently to treatment. For many years, researchers have used standard two-dimensional cell cultures to evaluate drug efficacy and understand the cellular and molecular biology of this disease, but 2D cultures have limitations compared to 3D cultures when it comes to mimicking the tumor microenvironment in the body. Rodent models are often used to understand melanoma progression and develop new effective treatments, but they do not accurately represent human physiology. Ex vivo modelling of melanoma could significantly improve our understanding and predict treatment outcomes. Efforts have been directed toward developing reliable models that accurately mimic melanoma in its appropriate tissue environment, including spheroid formation, tumor organoids, bio-printed tissue constructs, and microfluidic devices. This review provides a comprehensive exploration of 3D models used in drug screening for targeted therapy in melanoma by screening 120 studies and critically discussing 22 key research publications. Moreover, we provide details of drug screening accuracy and therapeutic efficacy of melanoma 3D models and identify current challenges to propose future directions for enhancing 3D model-based drug screening. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.