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Abstract：
Uveal melanoma (UM) is an aggressive and deadly neoplasm. In recent decades, great efforts have been made to obtain a more comprehensive understanding of genetics, genomics and molecular changes in UM, enabling the identification of key cellular processes and signalling pathways. Still, there is no effective treatment for the metastatic disease. Intratumoural heterogeneity (ITH) is thought to be one of the leading determinants of metastasis, therapeutic resistance and recurrence. Crucially, tumours are complex ecosystems, where cancer cells, and diverse cell types from their microenvironment engage in dynamic spatiotemporal crosstalk that allows cancer progression, adaptation and evolution. This highlights the urgent need to gain insight into ITH in UM and its intersection with the microenvironment to overcome treatment failure. Here we provide an overview of the studies and technologies to study ITH in human UMs and tumour micro-environmental composition. We discuss how to incorporate ITH into clinical consideration for the purpose of advocating for new clinical management. We focus on the application of single-cell transcriptomic analysis and propose that understanding the driving forces and functional consequences of the observed tumour heterogeneity holds promise for changing the treatment paradigm of metastatic UMs, surmounting resistance and improving patient prognosis.
摘要：
葡萄膜黑色素瘤（UM）是一种侵袭性和致命的肿瘤。近几十年来,已经做出了巨大的努力来获得对遗传学的更全面的理解，UM的基因组学和分子变化，能够识别关键的细胞过程和信号通路。尽管如此，转移性疾病没有有效的治疗方法。肿瘤内异质性（ITH）被认为是转移的主要决定因素之一，治疗抗性和复发。至关重要的是，肿瘤是复杂的生态系统,癌细胞，和不同的细胞类型从他们的微环境参与动态时空串扰，允许癌症进展，适应和进化。这凸显了迫切需要深入了解UM中的ITH及其与微环境的交集，以克服治疗失败。在这里，我们概述了在人类UM和肿瘤微环境组成中研究ITH的研究和技术。我们将讨论如何将ITH纳入临床考虑，以倡导新的临床管理。我们专注于单细胞转录组学分析的应用，并提出理解观察到的肿瘤异质性的驱动力和功能后果有望改变转移性UM的治疗范式。克服阻力，改善患者预后。
