Bridging the gap between testing and clinics exploring alternative pre-clinical models in melanoma research

Melanoma, the deadliest form of skin cancer, poses a significant clinical challenge for the development of effective treatments. Conventional in vivo animal studies have shown limited translational relevance to humans, raising strength to pre-clinical models for melanoma research. This review provides an in-depth analysis of alternative pre-clinical models including in vitro and ex vivo platforms such as reconstructed skin, spheroids, organoids, organotypic models, skin-on-a-chip, and bioprinting. Through a comprehensive analysis, the specific attributes, advantages, and limitations of each model are elucidated. It discusses the points related to the uniqueness advantages, from capturing complex interactions between melanoma cells and their microenvironment to enabling high-throughput drug screening and personalized medicine approaches. This review is structured covering firstly the roadmap to identify the co-occurrence of discovering new melanoma treatments and the development of its models, secondly it covers a comparative between the most used models followed by a section discussing each of them: the in vitro and ex vivo models. It intends to serve as an asset for researchers of melanoma field and clinicians involved in melanoma therapy, offering insights into the diverse preclinical models available for optimizing their integration into the translational pipeline.