Rodrigues Joana G, Duarte Henrique O, Reis Celso A, Gomes Joana
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.
IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal.
Biochem Soc Trans. 2021 Apr 30;49(2):843-854. doi: 10.1042/BST20200763.
Aberrant cell surface glycosylation signatures are currently known to actively drive the neoplastic transformation of healthy cells. By disrupting the homeostatic functions of their protein carriers, cancer-associated glycans mechanistically underpin several molecular hallmarks of human malignancy. Furthermore, such aberrant glycan structures play key roles in the acquisition of molecular resistance to targeted therapeutic agents, which compromises their clinical efficacy, by modulating tumour cell aggressiveness and supporting the establishment of an immunosuppressive microenvironment. Recent advances in the study of the tumour cell glycoproteome have unravelled previously elusive molecular mechanisms of therapeutic resistance, guided the rational design of novel personalized therapeutic strategies, and may further improve the clinical performance of currently approved anti-cancer targeted agents. In this review, we highlight the impact of glycosylation in cancer targeted therapy, with particular focus on receptor tyrosine kinase-targeted therapy, immune checkpoints blockade therapy, and current developments on therapeutic strategies directed to glycan-binding proteins and other innovative glycan therapeutic strategies.
目前已知异常的细胞表面糖基化特征会积极推动健康细胞的肿瘤转化。通过破坏其蛋白质载体的稳态功能，癌症相关聚糖在机制上支撑了人类恶性肿瘤的几个分子特征。此外，这种异常的聚糖结构通过调节肿瘤细胞的侵袭性并支持免疫抑制微环境的建立，在获得对靶向治疗药物的分子抗性方面发挥关键作用，而这会损害它们的临床疗效。肿瘤细胞糖蛋白质组研究的最新进展揭示了以前难以捉摸的治疗抗性分子机制，指导了新型个性化治疗策略的合理设计，并可能进一步改善目前已获批的抗癌靶向药物的临床性能。在这篇综述中，我们强调糖基化在癌症靶向治疗中的影响，特别关注受体酪氨酸激酶靶向治疗、免疫检查点阻断治疗，以及针对聚糖结合蛋白的治疗策略和其他创新聚糖治疗策略的当前进展。
