Our understanding of the complex, adaptive mechanisms of response to targeted therapies in metastatic melanoma is now leading to more effective combination treatments. These include the simultaneous inhibition of signalling pathways and metabolic programmes, as well as epigenetic mechanisms or immunological checkpoints. We review the latest pre-clinical and clinical results of strategies to delay tumor progression through combination approaches, and also highlight some of the problems ahead, including patient stratification, the complexity of targeting adaptive responses, and the management of more severe toxicities that result from double and triple-drug treatments.

中文翻译：

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针对黑色素瘤治疗中的复杂适应性反应。

我们对转移性黑色素瘤靶向治疗的复杂，适应性机制的了解目前正在导致更有效的联合治疗。这些包括同时抑制信号传导途径和代谢程序，以及表观遗传机制或免疫学检查要点。我们回顾了通过联合方法延缓肿瘤进展的策略的最新临床前和临床结果，并重点介绍了未来存在的一些问题，包括患者分层，靶向适应性反应的复杂性以及因以下原因导致的更严重毒性的管理双重和三重药物治疗。