Growth factors and oncogenes as targets in melanoma: lost in translation?
Growth factors and oncogenes as targets in melanoma: lost in translation?
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DOI：
10.1016/j.yadr.2007.07.015
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发表时间：
2007-01-01
期刊：
影响因子：
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通讯作者：
Wagner, Stephan N
中科院分区：
文献类型：
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作者：
Kwong, Lawrence;Chin, Lynda;Wagner, Stephan N
如果在早期不进行治疗，黑色素瘤会成为一种高度侵袭性的癌症，并会迅速转移到远处。尽管细胞生物学分析已经发现了许多与黑色素瘤发生和发展有关的信号通路-包括MAPK、PI3K和FAK通路-但针对这些细胞成分的有效治疗仍然难以找到。全基因组技术，如微阵列芯片和阵列比较基因组杂交，已经产生了遗传信息，可以确定对诱导和维持恶性表型至关重要的细胞机制。因此，这些数据可以指导生物相关药物的选择。然而，这些技术也将黑色素瘤确定为一种在遗传和生物上高度异质性的疾病，可能需要根据患者？S的个人基因和生物改变进行个性化定制治疗。此外，这些技术已经产生了大量关于候选黑色素瘤基因的数据，这些数据等待广泛的功能验证，以区分所谓的“司机”和“乘客”事件。在这篇综述中，我们包括黑色素瘤治疗的几个进展及其目前的局限性，以及新出现的基因组、蛋白质组和表观遗传学策略，以识别可能有助于治疗靶向的关键细胞依赖性。
If untreated at early stages, melanoma becomes a highly aggressive cancer with rapid metastasis to distant sites. Although cell biologic analyses have uncovered a multitude of signaling pathways involved in melanoma genesis and progression – including the MAPK, PI3K, and FAK pathways – efficacious therapies that target these cellular components have remained elusive. Genome-wide technologies such as microarray chips and array comparative genomic hybridization have generated genetic information that can identify cellular mechanisms critical for the induction and maintainence of the malignant phenotype. Thus, such data can guide the choice of a biologically relevant drug. However, these techniques have also identified melanoma as a genetically and biologically highly heterogeneous disease that likely requires individually tailored therapies based on the patient¹s individual genetic and biologic alterations. In addition, these techniques have generated a large body of data on candidate melanoma genes that await extensive functional validation to separate so called “driver” from “passenger” events. In this review, we cover several advances in melanoma therapeutics and their current limitations as well as emerging genomic, proteomic, and epigenetic strategies for the identification of critical cellular dependencies that may be tractable to therapeutic targeting.