Targeting drivers of melanoma with synthetic small molecules and phytochemicals.
Targeting drivers of melanoma with synthetic small molecules and phytochemicals.
复制标题
DOI：
10.1016/j.canlet.2015.01.016
复制
发表时间：
2015-04-01
期刊：
影响因子：
9.7
通讯作者：
Afaq F
中科院分区：
文献类型：
--
作者：
Strickland LR;Pal HC;Elmets CA;Afaq F
黑色素瘤是最不常见的皮肤癌，但它是大多数皮肤癌死亡的原因。传统的治疗剂和免疫调节剂对转移性黑色素瘤没有显示出很大的疗效。靶向RAS/RAF/MEK/ERK（MAPK）信号通路的药物-BRAF抑制剂vemurafenib和dabrafenib，以及MEK 1/2抑制剂曲美替尼-增加了转移性黑色素瘤患者的生存率。此外，对于转移性黑素瘤的治疗，达拉非尼和曲美替尼的组合已显示出优于单一药剂疗法的上级。然而，对这些药剂的耐药性迅速发展。靶向MAPK、PI 3 K/AKT/mTOR（PI 3 K）、c-kit和其他信号传导途径的其他药剂和组合的研究目前正在进行中。此外，植物化学物质的研究已经通过靶向在黑色素瘤形成中具有既定作用的信号通路而产生了对抗增殖、存活、侵袭和转移的有希望的结果。植物化学物质相对较低的毒性使其辅助使用成为一种有吸引力的治疗选择。需要改善目前的黑色素瘤治疗的疗效，要求进一步研究这些策略中的每一个。本文就合成小分子抑制剂、联合治疗以及植物化学治疗的最新进展作一综述。
Melanoma is the least common form of skin cancer, but it is responsible for the majority of skin cancer deaths. Traditional therapeutics and immunomodulatory agents have not shown much efficacy against metastatic melanoma. Agents that target the RAS/RAF/MEK/ERK (MAPK) signaling pathway—the BRAF inhibitors vemurafenib and dabrafenib, and the MEK1/2 inhibitor trametinib—have increased survival in patients with metastatic melanoma. Further, the combination of dabrafenib and trametinib has been shown to be superior to single agent therapy for the treatment of metastatic melanoma. However, resistance to these agents develops rapidly. Studies of additional agents and combinations targeting the MAPK, PI3K/AKT/mTOR (PI3K), c-kit, and other signaling pathways are currently underway. Furthermore, studies of phytochemicals have yielded promising results against proliferation, survival, invasion, and metastasis by targeting signaling pathways with established roles in melanomagenesis. The relatively low toxicities of phytochemicals make their adjuvant use an attractive treatment option. The need for improved efficacy of current melanoma treatments calls for further investigation of each of these strategies. In this review, we will discuss synthetic small molecule inhibitors, combined therapies and current progress in the development of phytochemical therapies.