Department of Biomedical Engineering, Gachon University, Seongnam, 13120, Republic of Korea.
Central R & D Center, Medical & Bio Decision (MBD) Co., Ltd, Suwon, 16229, Republic of Korea.
J Exp Clin Cancer Res. 2023 Nov 22;42(1):309. doi: 10.1186/s13046-023-02899-4.
Recently, cancer organoid-based drug sensitivity tests have been studied to predict patient responses to anticancer drugs. The area under curve (AUC) or IC value of the dose-response curve (DRC) is used to differentiate between sensitive and resistant patient's groups. This study proposes a multi-parameter analysis method (cancer organoid-based diagnosis reactivity prediction, CODRP) that considers the cancer stage and cancer cell growth rate, which represent the severity of cancer patients, in the sensitivity test.
On the CODRP platform, patient-derived organoids (PDOs) that recapitulate patients with lung cancer were implemented by applying a mechanical dissociation method capable of high yields and proliferation rates. A disposable nozzle-type cell spotter with efficient high-throughput screening (HTS) has also been developed to dispense a very small number of cells due to limited patient cells. A drug sensitivity test was performed using PDO from the patient tissue and the primary cancer characteristics of PDOs were confirmed by pathological comparision with tissue slides.
The conventional index of drug sensitivity is the AUC of the DRC. In this study, the CODRP index for drug sensitivity test was proposed through multi-parameter analyses considering cancer cell proliferation rate, the cancer diagnosis stage, and AUC values. We tested PDOs from eight patients with lung cancer to verify the CODRP index. According to the anaplastic lymphoma kinase (ALK) rearrangement status, the conventional AUC index for the three ALK-targeted drugs (crizotinib, alectinib, and brigatinib) did not classify into sensitive and resistant groups. The proposed CODRP index-based drug sensitivity test classified ALK-targeted drug responses according to ALK rearrangement status and was verified to be consistent with the clinical drug treatment response.
Therefore, the PDO-based HTS and CODRP index drug sensitivity tests described in this paper may be useful for predicting and analyzing promising anticancer drug efficacy for patients with lung cancer and can be applied to a precision medicine platform.
最近，基于癌症类器官的药物敏感性测试已被用于预测患者对抗癌药物的反应。曲线下面积（AUC）或剂量反应曲线（DRC）的 IC 值用于区分敏感和耐药患者群体。本研究提出了一种多参数分析方法（基于癌症类器官的诊断反应预测，CODRP），该方法在敏感性测试中考虑了癌症分期和癌细胞生长速度，这代表了癌症患者的严重程度。
在 CODRP 平台上，通过应用一种能够实现高产量和高增殖率的机械解离方法，实现了对肺癌患者的类器官重现。还开发了一种一次性喷嘴式细胞点样器，由于患者细胞数量有限，该点样器具有高效的高通量筛选（HTS）能力。对患者组织来源的类器官进行药物敏感性测试，并通过与组织切片的病理比较来确认类器官的原发性癌症特征。
药物敏感性的传统指标是 DRC 的 AUC。在本研究中，通过考虑癌细胞增殖率、癌症诊断阶段和 AUC 值的多参数分析，提出了用于药物敏感性测试的 CODRP 指数。我们测试了 8 名肺癌患者的类器官，以验证 CODRP 指数。根据间变性淋巴瘤激酶（ALK）重排状态，三种 ALK 靶向药物（克唑替尼、阿来替尼和布加替尼）的传统 AUC 指数不能将其分为敏感和耐药组。基于 CODRP 指数的药物敏感性测试根据 ALK 重排状态对 ALK 靶向药物的反应进行分类，并与临床药物治疗反应一致。
因此，本文中描述的基于类器官的 HTS 和 CODRP 指数药物敏感性测试可能有助于预测和分析肺癌患者有前景的抗癌药物疗效，并可应用于精准医疗平台。
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