Qingxue Meng, Fengxu Yan, Chenchen You, Ruzhong Xu, Taixing Jing, Danyang Ni, Chenyang Hou, Dandan Xu, Shan Liu, Fei Guo, Zhongwu Li, Rensen Ran, Weizheng Liang
Rare melanoma subtypes, such as uveal melanoma, desmoplastic melanoma, mucosal melanoma, and acral melanoma, account for about 10% of all melanomas and exhibit unique genetic backgrounds and immune microenvironments, leading to poor clinical prognosis. Due to their low incidence and limited clinical samples, research and therapeutic strategies for these subtypes remain challenging. This review summarizes the current animal models used for rare melanoma, including spontaneous models, inducible models, genetically engineered models, and xenograft models. Each model has its unique advantages, but also has its own limitations in terms of genetic accuracy, microenvironment simulation, or applicability to immunotherapy research. Future advancements in technology should enhance multi-dimensional simulations of both genetics and the microenvironment, thus promoting mechanistic research and the development of precision therapeutic strategies for rare melanoma.