Duarte Henrique Oliveira, Reis Celso Albuquerque, Blanchard Veronique, Tauber Rudolf
Instituto de Investigação e Inovação em Saúde, Universidade do Porto (i3S), Porto, Portugal.
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal.
Handb Exp Pharmacol. 2025;288:243-293. doi: 10.1007/164_2025_751.
Structural alterations of the glycan chains attached to glycoproteins and glycolipids are present in all types of malignomas investigated to date, including adenocarcinomas, sarcomas and haematological malignancies. They occur in humans as well as in animals including experimental models of malignancy, regardless of the type, cause, or stage of the tumour. The biochemical and genomic characterization of the enzymatic machineries involved in glycan biosynthesis in cancer cells shows that tumour-associated glycosylation changes are a critical part of tumour initiation and progression. Experimental studies and epidemiological findings give clear evidence that tumour-associated glycans bear functional significance in the invasive and metastatic growth of malignancies, for immunological tumour defence and, hence, influence the clinical outcome and the prognosis of cancer patients. Tumour-associated glycan changes are, moreover, targets for new pharmacological and immunological therapy methods and serve as important clinical biomarkers for diagnosis, particularly for monitoring disease progression and therapeutic efficacy. This chapter provides an overview of the major types of changes of glycosylation, genetic and biochemical mechanisms contributing to cancer-associated glycosylation, functional consequences for tumour growth and the clinical significance in cancer diagnosis, monitoring and treatment.
迄今为止,在所有已研究的恶性肿瘤类型中,包括腺癌、肉瘤和血液系统恶性肿瘤,都存在与糖蛋白和糖脂相连的聚糖链结构改变。无论肿瘤的类型、病因或阶段如何,这些改变在人类以及包括恶性肿瘤实验模型在内的动物中均会出现。对癌细胞中参与聚糖生物合成的酶机制进行的生化和基因组特征分析表明,肿瘤相关的糖基化变化是肿瘤发生和发展的关键部分。实验研究和流行病学研究结果清楚地表明,肿瘤相关聚糖在恶性肿瘤的侵袭和转移生长、免疫肿瘤防御中具有功能意义,因此会影响癌症患者的临床结局和预后。此外,肿瘤相关的聚糖变化是新的药理学和免疫治疗方法的靶点,并且作为重要的临床生物标志物用于诊断,特别是用于监测疾病进展和治疗效果。本章概述了糖基化变化的主要类型、导致癌症相关糖基化的遗传和生化机制、对肿瘤生长的功能影响以及在癌症诊断、监测和治疗中的临床意义。