The ribosome in eukaryotic cells is a macromolecular complex composed of four ribonucleic acids and over 80 proteins. This organelle facilitates protein synthesis in cells, and its activity is strongly upregulated in human cancers. Immune cells, a variety of cellular stressors and numerous structurally and mechanistically distinct anti-cancer agents have been shown to induce ribosomal RNA degradation in tumour cells in vitro and in vivo—a phenomenon we termed “RNA disruption”. RNA disruption can be quantified in cultured cell lines and patient samples using the RNA disruption assay (RDA). Unlike well-known high-throughput anti-cancer drug sensitivity assays, RDA can distinguish between dying and arrested tumour cells, making it an attractive assay for anti-cancer drug discovery and development. Low tumour RNA disruption during neoadjuvant chemotherapy (as measured using RDA) is strongly associated with residual disease and reduced disease-free survival, making it a potentially valuable chemo-resistance assessment tool. High RNA disruption may also indicate chemo-responsiveness. RDA holds the prospect of being a useful tool to escalate or de-escalate neoadjuvant chemotherapy in cancer patients. Moreover, the assay’s ability to predict treatment outcomes during neoadjuvant chemotherapy may permit its use in adaptive clinical trials and in drug approval by regulatory agencies. This review provides insight into the cellular processes involved in chemotherapy-induced RNA disruption. It also describes the results of clinical studies on tumour RNA disruption in cancer patients and suggests possible approaches that could be considered for the utilization of RDAs in the clinical management of breast cancer patients undergoing current neoadjuvant chemotherapy regimens.
真核细胞中的核糖体是由四种核糖核酸和80多种蛋白质组成的大分子复合物。该细胞器促进细胞内的蛋白质合成，其活性在人类癌症中显著上调。研究表明，免疫细胞、多种细胞应激源以及大量结构和机制各异的抗癌药物能够在体外和体内诱导肿瘤细胞发生核糖体RNA降解——我们将这一现象称为"RNA断裂"。通过RNA断裂检测法（RDA）可在培养细胞系和患者样本中对RNA断裂进行定量分析。与已知的高通量抗癌药物敏感性检测不同，RDA能够区分凋亡与停滞的肿瘤细胞，这使其成为抗癌药物研发中极具吸引力的检测手段。新辅助化疗期间较低的肿瘤RNA断裂水平（通过RDA测定）与残留病灶及无病生存期缩短密切相关，使其成为潜在有价值的化疗耐药评估工具。而高RNA断裂水平可能提示化疗敏感性。RDA有望成为调整癌症患者新辅助化疗强度的有效工具。此外，该检测方法在新辅助化疗期间预测治疗结局的能力，可能使其适用于适应性临床试验及监管机构的药物审批。本综述深入探讨了化疗诱导RNA断裂所涉及的细胞过程，阐述了癌症患者肿瘤RNA断裂的临床研究结果，并提出了在当前新辅助化疗方案下，将RDA应用于乳腺癌患者临床管理的可行途径。
肿瘤(癌症)患者之家