Skin Carcinogenesis Laboratory, Queensland Institute of Medical Research, Herston, Qld, Australia.
Pigment Cell Melanoma Res. 2011 Dec;24(6):1158-76. doi: 10.1111/j.1755-148X.2011.00923.x. Epub 2011 Nov 2.
Phenotypic and molecular heterogeneity in human melanoma has impaired efforts to explain many of the clinically important features of melanoma. For example, many of the underlying mechanisms that might predict age-of-onset, time to metastasis and other key elements in melanoma progression remain unknown. Furthermore, melanoma staging used to predict outcome and treatment has not yet moved beyond a basic phenotypic classification. While molecularly targeted therapies show great promise for melanoma patients, establishing accurate animal models that recapitulate human cutaneous melanoma progression remains a priority. We examine the relevance of mice as models for human melanoma progression and for key molecular and histopathologic variants of melanoma. These mice may be used as preclinical models to probe the relationships between causative mutations, disease progression and outcome for molecularly targeted therapeutics. We ask how new mouse models, or more detailed histopathologic and molecular analyses of existing mouse models, may be used to advance our understanding of genotype-phenotype correlations in this tumour type. This necessarily involves a consideration of the utility of mice as models for ultraviolet radiation-induced melanoma, and how this might be improved.
人类黑色素瘤的表型和分子异质性，使得许多与黑色素瘤临床相关的重要特征难以解释。例如，许多可能预测发病年龄、转移时间和黑色素瘤进展其他关键因素的潜在机制仍然未知。此外，用于预测预后和治疗的黑色素瘤分期尚未超越基本的表型分类。虽然分子靶向疗法对黑色素瘤患者有很大的希望，但建立能够重现人类皮肤黑色素瘤进展的准确动物模型仍然是当务之急。我们检查了小鼠作为人类黑色素瘤进展模型以及黑色素瘤关键分子和组织病理学变异模型的相关性。这些小鼠可被用于临床前模型，以探究导致突变、疾病进展和分子靶向治疗结果之间的关系。我们还探讨了新的小鼠模型，或对现有小鼠模型进行更详细的组织病理学和分子分析，如何能帮助我们更好地理解该肿瘤类型的基因型-表型相关性。这必然需要考虑到小鼠作为紫外线诱导黑色素瘤模型的实用性，以及如何改进这一模型。
