Precision Oncology in Melanoma: Changing Practices.

Sean C Dougherty, William L Flowers, Elizabeth M Gaughan
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Abstract

Over the last 2 decades, significant progress has been made in our understanding of the genomics, tumor immune microenvironment, and immunogenicity of malignant melanoma. Historically, the prognosis for metastatic melanoma was poor because of limited treatment options. However, after multiple landmark clinical trials displaying the efficacy of combined BRAF/MEK inhibition for BRAF-mutant melanoma and the application of immune checkpoint inhibitors targeting the programmed death-1, cytotoxic T-lymphocyte antigen-4, and lymphocyte activation gene-3 molecules, overall survival rates have dramatically improved. The role of immune checkpoint inhibition has since expanded to the neoadjuvant and adjuvant settings with multiple regimens in routine use. Personalized therapies, including tumor-infiltrating lymphocytes that are extracted from a patient's melanoma and eventually reinfused into the patient, and messenger RNA vaccines used to target neoantigens unique to a patient's tumor, show promise. Improvements in accompanying imaging modalities, particularly within the field of nuclear medicine, have allowed for more accurate staging of disease and assessment of treatment response. Continued growth in the role of nuclear medicine in the evaluation of melanoma, including the incorporation of artificial intelligence into image interpretation and use of radiolabeled tracers allowing for intricate imaging of the tumor immune microenvironment, is expected in the coming years.

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黑色素瘤的精准肿瘤学:改变实践。
过去二十年来,我们对恶性黑色素瘤的基因组学、肿瘤免疫微环境和免疫原性的了解取得了重大进展。由于治疗方案有限,转移性黑色素瘤的预后一直不佳。然而,在多项具有里程碑意义的临床试验显示 BRAF/MEK 联合抑制 BRAF 突变黑色素瘤的疗效,以及针对程序性死亡-1、细胞毒性 T 淋巴细胞抗原-4 和淋巴细胞活化基因-3 分子的免疫检查点抑制剂的应用之后,总体生存率得到了显著改善。此后,免疫检查点抑制的作用已扩展到新辅助治疗和辅助治疗,并有多种治疗方案被常规使用。个性化疗法,包括从患者黑色素瘤中提取并最终回输到患者体内的肿瘤浸润淋巴细胞,以及用于靶向患者肿瘤特有新抗原的信使 RNA 疫苗,都显示出了良好的前景。伴随成像模式的改进,尤其是核医学领域的改进,使疾病分期和治疗反应评估更加准确。预计未来几年,核医学在黑色素瘤评估中的作用将继续增强,包括将人工智能融入图像解读,以及使用放射性标记示踪剂对肿瘤免疫微环境进行复杂成像。
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