Table 3.

Main melanoma murine models: advantages and disadvantages.

Experimental Model	Advantages	Disadvantages	References
Syngeneic	Functional immune system. Fast and easy to establish Tumor interaction with the microenvironment Metastasis formation Both tumor cells and mouse with the same genetic background	Less predictive for clinical translation Different anatomy, physiology and biochemistry compared to human (e.g., adhesion proteins and growth factors) Not properly reproducing the interactions between cancer cells and the immune system Limited availability of cell lines Rapid and uncontrolled cell growth	[73,90,109,186]
Xenograft	Use of human tumor samples Heterogeneity Metastasis formation Simple to accomplish Possibilities for “co-clinical trials” Study of drug resistance Large number of available human cell lines Tumors are easily and precisely measured	Time-consuming Expensive (compared with immunocompetent mice) Lack of immune system Poorly predictive of clinical outcomes Lack of standardized and reproducible protocols and inadequacy to study the early phases of tumor growth (PDX models) Different tumor evolution as compared to parental lesion	[90,109,181,186]
Genetically Engineered	Specific gene mutation Combination of multiple gene mutations Functional immune system Stepwise tumor progression Phenotypic, histological, and genetic similarities to human counterparts Modulation of human cancer under physiological conditions Tumors develop in the tissue of origin	Inability to replicate the characteristics of the advanced melanoma Expensive, time-consuming and labor intensive Different anatomy, physiology, and biochemistry (mouse versus human) Lack of different genetic background and tissue-specific promoters Asynchronous development of tumors. Heterogeneity Restricted use due to intellectual property rights and patents	[90,109,181,186,203,204]
Radiation-induced	Useful for studying the risk factors, pathogenesis and development of human melanoma	Long time for tumor development High costs in animal maintenance/care Lack of responsiveness by mice Histologically and anatomically different from human melanoma	[186]
Carcinogen-induced	Simple to accomplish The tumors are easily visualized, not requiring invasive processes for tumor monitoring Recapitulate the time-dependent and multi-stage progression of tumor pathogenesis Functional immune system Can be used in combination with other models	Repeated use of carcinogenic agents Outbred mice with non-uniform genetic backgrounds and varied sensitivity to carcinogens Nonpigmented lesions when melanoma is induced by certain carcinogenic agents Not clinically relevant for human melanoma	[185,186,203,205]