de Souza Camila Ferreira, Morais Alice Santana, Jasiulionis Miriam Galvonas
Pharmacology Department, Federal University of São Paulo, 04039-032 São Paulo, SP, Brazil.
Dermatol Res Pract. 2012;2012:156068. doi: 10.1155/2012/156068. Epub 2011 Oct 31.
Melanoma is a human neurocristopathy associated with developmental defects in the neural crest-derived epidermal melanocytes. At the present time, at least three hypotheses were identified that may explain melanoma aetiology, as follows: (1) a model of linear progression from differentiated melanocytes to metastatic cancer cells (2) a model involving the appearance of melanoma stem-like cells, and (3) an epigenetic progenitor model of cancer. Treating metastatic melanoma is one of the most serious challenges in the 21st century. This is justified because of a subpopulation of cells presenting a remarkable molecular heterogeneity, which is able to explain the drug resistance and the growing mortality rates worldwide. Fortunately, there are now evidences sustaining the importance of genetic, epigenetic, and metabolomic alterations as biomarkers for classification, staging, and better management of melanoma patients. To illustrate some fascinating insights in this field, the genes BRAF(V600E) and CTLA4 have been recognized as bona fide targets to benefit melanoma patients. Our research attempts to carefully evaluate data from the literature in order to highlight the link between a molecular disease model and the key contribution of biomarkers in treating malignant melanoma metastases.
黑色素瘤是一种与神经嵴来源的表皮黑素细胞发育缺陷相关的人类神经嵴病。目前，已确定至少三种可能解释黑色素瘤病因的假说，如下：（1）从分化的黑素细胞到转移性癌细胞的线性进展模型；（2）涉及黑色素瘤干细胞样细胞出现的模型；（3）癌症的表观遗传祖细胞模型。治疗转移性黑色素瘤是21世纪最严峻的挑战之一。这是合理的，因为存在一群具有显著分子异质性的细胞，这能够解释耐药性以及全球范围内不断上升的死亡率。幸运的是，现在有证据支持基因、表观遗传和代谢组学改变作为黑色素瘤患者分类、分期及更好管理的生物标志物的重要性。为了阐述该领域一些引人入胜的见解，基因BRAF（V600E）和CTLA4已被确认为使黑色素瘤患者受益的真正靶点。我们的研究试图仔细评估文献数据，以突出分子疾病模型与生物标志物在治疗恶性黑色素瘤转移中的关键作用之间的联系。
