Jenkins Russell W, Sullivan Ryan J
Massachusetts General Hospital Cancer Center, Boston, MA, USA.
Melanoma Manag. 2016 Mar;3(1):47-59. doi: 10.2217/mmt.15.40. Epub 2016 Feb 17.
Melanoma is the deadliest form of skin cancer and the incidence continues to rise in the United States and worldwide. Activating mutations in oncogenes are found in roughly a third of all human cancers. Mutations in occur in approximately a fifth of cutaneous melanomas and are associated with aggressive clinical behavior. Cells harboring oncogenic mutations exhibit activation of multiple signaling cascades, including PI3K/Akt, MEK-ERK and RAL, which collectively stimulate cancer growth. While strategies to target N-Ras itself have proven ineffective, targeting one or more N-Ras effector pathways has shown promise in preclinical models. Despite promising preclinical data, current therapies for mutant melanoma remain limited. Immune checkpoint inhibitors and targeted therapies for mutant melanoma are transforming the treatment of metastatic melanoma, but the ideal treatment for mutant melanoma remains unknown. Improved understanding of mutant melanoma and relevant N-Ras effector signaling modules will be essential to develop new treatment strategies.
黑色素瘤是最致命的皮肤癌形式，在美国和全球范围内其发病率都在持续上升。致癌基因中的激活突变在大约三分之一的人类癌症中被发现。在大约五分之一的皮肤黑色素瘤中存在突变，并且与侵袭性临床行为相关。携带致癌突变的细胞表现出多种信号级联的激活，包括PI3K/Akt、MEK-ERK和RAL，这些共同刺激癌症生长。虽然靶向N-Ras本身的策略已被证明无效，但靶向一个或多个N-Ras效应通路在临床前模型中已显示出前景。尽管临床前数据很有前景，但目前针对突变型黑色素瘤的治疗仍然有限。免疫检查点抑制剂和针对突变型黑色素瘤的靶向治疗正在改变转移性黑色素瘤的治疗方式，但突变型黑色素瘤的理想治疗方法仍然未知。更好地理解突变型黑色素瘤和相关的N-Ras效应信号模块对于开发新的治疗策略至关重要。
