Lin Lehang, Lin De-Chen
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen University, Guangzhou 510120, China.
Cancers (Basel). 2019 Aug 12;11(8):1156. doi: 10.3390/cancers11081156.
Esophageal squamous cell carcinoma (ESCC) is a common and aggressive malignancy, with hitherto dismal clinical outcome. Genomic analyses of patient samples reveal a complex heterogeneous landscape for ESCC, which presents in both intertumor and intratumor forms, manifests at both genomic and epigenomic levels, and contributes significantly to tumor evolution, drug resistance, and metastasis. Here, we review the important molecular characteristics underlying ESCC heterogeneity, with an emphasis on genomic aberrations and their functional contribution to cancer evolutionary trajectories. We further discuss how novel experimental tools, including single-cell sequencing and three-dimensional organoids, may advance our understanding of tumor heterogeneity. Lastly, we suggest that deciphering the mechanisms governing tumor heterogeneity holds the potential to developing precision therapeutics for ESCC patients.
食管鳞状细胞癌（ESCC）是一种常见且侵袭性强的恶性肿瘤，临床预后迄今不容乐观。对患者样本的基因组分析揭示了ESCC复杂的异质性格局，这种异质性以肿瘤间和肿瘤内两种形式存在，在基因组和表观基因组水平均有体现，并对肿瘤进展、耐药性和转移有显著影响。在此，我们综述了ESCC异质性背后的重要分子特征，重点关注基因组畸变及其对癌症进化轨迹的功能贡献。我们还讨论了包括单细胞测序和三维类器官在内的新型实验工具如何能增进我们对肿瘤异质性的理解。最后，我们认为破解调控肿瘤异质性的机制有望为ESCC患者开发精准疗法。
