The Molecular Oncology Program and Comprehensive Melanoma Research Center, The Moffitt Cancer Center, Tampa, Florida, USA.
J Invest Dermatol. 2010 Jan;130(1):28-37. doi: 10.1038/jid.2009.177.
Despite years of research, there has been little improvement in survival for patients with disseminated melanoma. Recent work has identified mutations in BRAF and NRAS, leading to constitutive mitogen-activated protein kinase (MAPK) pathway as well as constitutive activity in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, as being critical events in melanoma growth and progression. In the current review, we discuss how these complex mutational and signaling profiles can be understood using a network biology approach, and suggest how an understanding of the key signaling nodes involved in progression and survival will lead to improvements in melanoma therapy.
尽管经过多年的研究,患有转移性黑色素瘤的患者的生存率几乎没有提高。最近的研究已经确定了 BRAF 和 NRAS 突变,导致有丝分裂原激活的蛋白激酶(MAPK)途径以及磷酸肌醇 3-激酶(PI3K)/蛋白激酶 B(AKT)途径的组成性活性,这些都是黑色素瘤生长和进展的关键事件。在本综述中,我们讨论了如何使用网络生物学方法来理解这些复杂的突变和信号谱,并提出了对参与进展和存活的关键信号节点的理解将如何导致黑色素瘤治疗的改善。