Minimal Residual Disease Laboratory, Faculty of Medicine, University Finis Terrae, Santiago, Chile.
Adv Clin Chem. 2024;119:33-70. doi: 10.1016/bs.acc.2024.02.002. Epub 2024 Feb 24.
Minimal residual disease (MRD) has been defined as a very small numbers of cancer cells that remain in the body after curative treatment. Its presence or absence will ultimately determine prognosis. With the introduction of new technologies the presence of MRD in patients with solid tumours can be detected and characterized. As MRD predicts future relapse, be it early or late treatment failure, in an otherwise asymptomatic patient its treatment and when to start treatment remains to be determined. Thus the concepts of personalized medicine using different biomarkers to classify the biological properties of MRD maybe come possible. Based on this determinations it may be possible to use targeted therapies rather than all patients with the same type of cancer receiving a standard treatment. However, it is important to understand the limitations of the different technologies, what these techniques are detecting and how they may help in the treatment of patients with cancer. The majority of published studies are in patients with metastatic cancer and there are few reports in patients with MRD. In this chapter the concept of MRD, the methods used to detect it and what treatments may be effective based on the biological characteristics of the tumour cells as determined by different biomarkers is reviewed. MRD depends on the phenotypic properties of the tumour cells to survive in their new environment and the anti-tumour immune response. This is a dynamic process and changes with time in the wake of immunosuppression caused by the tumour cells and/or the effects of treatment to select resistant tumour cells. With the use of biomarkers to typify the characteristics of MRD and the development of new drugs a personalized treatment can be designed rather than all patients given the same treatment. Patients who are initially negative for MRD may not require further treatment with liquid biopsies used to monitor the patients during follow-up in order to detect those patients who may become MRD positive. The liquid biopsy used during the follow up of MRD positive patients can be used to detect changes in the biological properties of the tumour cells and thus may need treatment changes to overcome tumour cell resistance.
微小残留病 (MRD) 被定义为在根治性治疗后体内仍然存在的少量癌细胞。它的存在与否最终将决定预后。随着新技术的引入，实体瘤患者的 MRD 可以被检测和特征化。由于 MRD 预测未来的复发，无论是早期还是晚期治疗失败，在没有其他症状的患者中，其治疗和何时开始治疗仍有待确定。因此，使用不同的生物标志物来分类 MRD 的生物学特性的个性化医学概念也许是可能的。基于这些确定，可能有可能使用靶向治疗而不是所有患有相同类型癌症的患者接受标准治疗。然而，重要的是要了解不同技术的局限性、这些技术正在检测什么以及它们如何帮助治疗癌症患者。大多数已发表的研究都在转移性癌症患者中进行，而在 MRD 患者中的报告很少。在这一章中，回顾了 MRD 的概念、用于检测它的方法以及根据不同生物标志物确定的肿瘤细胞的生物学特征，哪些治疗可能有效。MRD 取决于肿瘤细胞在新环境中生存的表型特性和抗肿瘤免疫反应。这是一个动态过程，随着肿瘤细胞引起的免疫抑制和/或治疗选择耐药肿瘤细胞的影响，随着时间的推移而变化。使用生物标志物来典型化 MRD 的特征，并开发新的药物，可以设计个性化的治疗方法，而不是所有患者都接受相同的治疗。最初 MRD 阴性的患者可能不需要进一步的治疗，因为液体活检可用于监测患者的随访情况，以检测那些可能成为 MRD 阳性的患者。在 MRD 阳性患者的随访中使用的液体活检可用于检测肿瘤细胞生物学特性的变化，因此可能需要治疗改变以克服肿瘤细胞耐药性。
