Cisplatin-based chemotherapeutic regimens are the most frequently used (neo)adjuvant treatments for the majority of solid tumors. While platinum-based chemotherapeutic regimens have proven effective against highly proliferative malignant tumors, significant relapse and progression rates as well as decreased overall survival are still observed. Currently, it is known that sub-populations of chemoresistant cells share biological properties with cancer stem cells (CSC), which are believed to be responsible for tumor relapse, invasion and ultimately disease dissemination through acquisition of mesenchymal cell traits. In spite of concentrated efforts devoted to decipher the mechanisms underlying CSC chemoresistance and to design targeted therapeutics to these cells, proteomics has failed to unveil molecular signatures capable of distinguishing between malignant and non-malignant stem cells. This has hampered substantial developments in this complex field. Envisaging a novel rationale for an effective therapy, the current review summarizes the main cellular and molecular mechanisms underlying cisplatin resistance and the impact of chemotherapy challenge in CSC selection and clinical outcome. It further emphasizes the growing amount of data supporting a role for protein glycosylation in drug resistance. The dynamic and context-dependent nature of protein glycosylation is also comprehensively discussed, hence highlighting its potentially important role as a biomarker of CSC. As the paradigm of cancer therapeutics shifts towards precision medicine and patient-tailored therapeutics, we bring into focus the need to introduce glycomics and glycoproteomics in holistic pan-omics models, in order to integrate diverse, multimodal and clinically relevant information towards more effective cancer therapeutics.

中文翻译：

---

顺铂耐药性和靶向癌干细胞的机制：在方程式中添加糖基化。

对于大多数实体瘤，基于顺铂的化疗方案是最常用的（新）辅助治疗。尽管已证明铂类化学疗法可有效治疗高度增生的恶性肿瘤，但仍观察到明显的复发和进展率以及降低的总生存率。当前，已知化学抗性细胞的亚群与癌症干细胞（CSC）具有生物学特性，据信这与通过获取间充质细胞性状导致肿瘤复发，侵袭和最终疾病传播有关。尽管已作出了巨大的努力来破译CSC化学抗性的机制并设计针对这些细胞的靶向治疗剂，蛋白质组学未能揭示能够区分恶性和非恶性干细胞的分子标记。这阻碍了这个复杂领域的实质性发展。考虑到一种有效疗法的新原理，本篇综述总结了顺铂耐药的主要细胞和分子机制以及化疗挑战对CSC选择和临床结果的影响。它进一步强调了越来越多的数据支持蛋白质糖基化在耐药性中的作用。蛋白质糖基化的动态和上下文相关性质也得到了全面讨论，因此突出了其作为CSC生物标记物的潜在重要作用。随着癌症疗法的范式向精密医学和患者定制疗法的转变，