Targeted therapy directed against oncogenic BRAF mutations and immune checkpoint inhibitors have transformed melanoma therapy over the past decade and prominently improved patient outcomes. However, not all patients will respond to targeted therapy or immunotherapy and many relapse after initially responding to treatment. This unmet need presents two major challenges. First, can we elucidate novel oncogenic drivers to provide new therapeutic targets? Second, can we identify patients who are most likely to respond to current therapeutic strategies in order to both more accurately select populations and avoid undue drug exposure in patients unlikely to respond? In an effort to evaluate the current state of the field with respect to these questions, we provide an overview of some common oncogenic mutations in patients with metastatic melanoma and ongoing efforts to therapeutically target these populations, as well as a discussion of biomarkers for response to immune checkpoint inhibitors-including tumor programmed death ligand 1 expression and the future use of neoantigens as a means of truly personalized therapy. This information is becoming important in treatment decision making and provides the framework for a treatment algorithm based on the current landscape in metastatic melanoma.

中文翻译：

---

靶向治疗和免疫治疗：转移性黑色素瘤中新兴的生物标志物。

在过去的十年中，针对致癌BRAF突变和免疫检查点抑制剂的靶向疗法已经改变了黑色素瘤疗法，并显着改善了患者的预后。但是，并非所有患者都会对靶向治疗或免疫治疗产生反应，并且许多患者在最初对治疗产生反应后就会复发。这种未满足的需求提出了两个主要挑战。首先，我们能否阐明新的致癌驱动因子以提供新的治疗靶点？其次，我们能否确定最有可能对当前治疗策略做出反应的患者，以便更准确地选择人群并避免不太可能做出反应的患者过度接触药物？为了评估有关这些问题的当前领域，我们概述了转移性黑色素瘤患者中的一些常见致癌突变，并针对这些人群进行了治疗性努力，并讨论了对免疫检查点抑制剂反应的生物标志物，包括肿瘤程序性死亡配体1表达和新抗原的未来应用作为真正个性化治疗的一种手段。这些信息在治疗决策中变得越来越重要，并为基于转移性黑素瘤的当前现状的治疗算法提供了框架。