Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
Nat Cancer. 2024 Jul;5(7):964-982. doi: 10.1038/s43018-024-00794-1. Epub 2024 Jul 17.
Metastatic melanoma is among the most enigmatic advanced cancers to clinically manage despite immense progress in the way of available therapeutic options and historic decreases in the melanoma mortality rate. Most patients with metastatic melanoma treated with modern targeted therapies (for example, BRAFV600E/K inhibitors) and/or immune checkpoint blockade (for example, anti-programmed death 1 therapy) will progress, owing to profound tumor cell plasticity fueled by genetic and nongenetic mechanisms and dichotomous host microenvironmental influences. Here we discuss the determinants of tumor heterogeneity, mechanisms of therapy resistance and effective therapy regimens that hold curative promise.
转移性黑色素瘤是最难临床管理的晚期癌症之一，尽管在治疗选择方面取得了巨大进展，且黑色素瘤死亡率呈历史性下降。大多数接受现代靶向治疗（例如，BRAFV600E/K 抑制剂）和/或免疫检查点阻断（例如，抗程序性死亡 1 治疗）的转移性黑色素瘤患者都会出现进展，这是由于遗传和非遗传机制以及二分宿主微环境影响所驱动的肿瘤细胞可塑性。在这里，我们讨论了肿瘤异质性的决定因素、治疗耐药机制以及具有治愈希望的有效治疗方案。
