Paluncic Jasmina, Kovacevic Zaklina, Jansson Patric J, Kalinowski Danuta, Merlot Angelika M, Huang Michael L-H, Lok Hiu Chuen, Sahni Sumit, Lane Darius J R, Richardson Des R
Molecular Pharmacology and, Pathology Program, Department of Pathology and, Bosch Institute,University of Sydney, Sydney, New South Wales, 2006, Australia.
Molecular Pharmacology and, Pathology Program, Department of Pathology and, Bosch Institute,University of Sydney, Sydney, New South Wales, 2006, Australia.
Biochim Biophys Acta. 2016 Apr;1863(4):770-84. doi: 10.1016/j.bbamcr.2016.01.025. Epub 2016 Feb 1.
Melanoma has markedly increased worldwide during the past several decades in the Caucasian population and is responsible for 80% of skin cancer deaths. Considering that metastatic melanoma is almost completely resistant to most current therapies and is linked with a poor patient prognosis, it is crucial to further investigate potential molecular targets. Major cell-autonomous drivers in the pathogenesis of this disease include the classical MAPK (i.e., RAS-RAF-MEK-ERK), WNT, and PI3K signaling pathways. These pathways play a major role in defining the progression of melanoma, and some have been the subject of recent pharmacological strategies to treat this belligerent disease. This review describes the latest advances in the understanding of melanoma progression and the major molecular pathways involved. In addition, we discuss the roles of emerging molecular players that are involved in melanoma pathogenesis, including the functional role of the melanoma tumor antigen, p97/MFI2 (melanotransferrin).
在过去几十年间，黑色素瘤在全球白种人群中的发病率显著上升，且占皮肤癌死亡病例的80%。鉴于转移性黑色素瘤几乎对目前的大多数治疗方法完全耐药，并且与患者预后不良相关，进一步研究潜在的分子靶点至关重要。该疾病发病机制中的主要细胞自主驱动因素包括经典的MAPK（即RAS-RAF-MEK-ERK）、WNT和PI3K信号通路。这些通路在定义黑色素瘤的进展中起主要作用，并且其中一些已成为近期治疗这种侵袭性疾病的药理学策略的研究对象。本综述描述了对黑色素瘤进展及相关主要分子通路理解的最新进展。此外，我们还讨论了参与黑色素瘤发病机制的新兴分子参与者的作用，包括黑色素瘤肿瘤抗原p97/MFI2（黑色素转铁蛋白）的功能作用。
