Prediction of therapeutic outcomes is important for cancer patients in order to reduce side effects and improve the efficacy of anti-cancer drugs. Currently, the most widely accepted method for predicting the efficacy of anti-cancer drugs is gene panel testing based on next-generation sequencing. However, gene panel testing has several limitations. For example, only 10% of cancer patients are estimated to have druggable mutations, even if whole-exome sequencing is applied. Additionally, even if optimal drugs are selected, a significant proportion of patients derive no benefit from the indicated drug treatment. Furthermore, most of the anti-cancer drugs selected by gene panel testing are molecularly targeted drugs, and the efficacies of cytotoxic drugs remain difficult to predict. Apart from gene panel testing, attempts to predict chemotherapeutic efficacy using ex vivo cultures from cancer patients have been increasing. Several groups have retrospectively demonstrated correlations between ex vivo drug sensitivity and clinical outcome. For ex vivo culture, surgically resected tumor tissue is the most abundant source. However, patients with recurrent or metastatic tumors do not usually undergo surgery, and chemotherapy may be the only option for those with inoperable tumors. Therefore, predictive methods using small amounts of cancer tissue from diagnostic materials such as endoscopic, fine-needle aspirates, needle cores and liquid biopsies are needed. To achieve this, various types of ex vivo culture and endpoint assays using effective surrogate biomarkers of drug sensitivity have recently been developed. Here, we review the variety of ex vivo cultures and endpoint assays currently available.
预测治疗效果对于癌症患者至关重要,旨在减少副作用并提高抗癌药物的疗效。目前,预测抗癌药物疗效最广泛接受的方法是基于下一代测序的基因组合检测。然而,基因组合检测存在若干局限性。例如,即使应用全外显子组测序,估计仅有约10%的癌症患者携带可药物靶向的突变。此外,即使选择了最佳药物,仍有相当比例的患者未能从指定药物治疗中获益。再者,通过基因组合检测选择的抗癌药物多为分子靶向药物,而细胞毒性药物的疗效仍难以预测。 除基因组合检测外,利用癌症患者离体培养物预测化疗疗效的尝试日益增多。多个研究团队已通过回顾性研究证实了离体药物敏感性与临床结果之间的相关性。在离体培养中,手术切除的肿瘤组织是最丰富的来源。然而,复发或转移性肿瘤患者通常不进行手术,对于无法手术的肿瘤患者,化疗可能是唯一选择。因此,需要开发能够利用少量诊断材料(如内镜活检、细针穿刺、针芯活检及液体活检)中癌组织进行预测的方法。为实现这一目标,近期已开发出多种类型的离体培养体系及采用药物敏感性有效替代生物标志物的终点检测方法。本文综述了当前可用的各类离体培养技术与终点检测方法。