In vitro evaluation of clinical activity and toxicity of anticancer drugs using tumor cells from patients and cells representing normal tissues
In vitro evaluation of clinical activity and toxicity of anticancer drugs using tumor cells from patients and cells representing normal tissues
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DOI：
10.1007/s00280-011-1746-1
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发表时间：
2012-03-01
影响因子：
3
通讯作者：
Lindhagen, Elin
中科院分区：
文献类型：
--
作者：
Haglund, Caroline;Aleskog, Anna;Lindhagen, Elin
目的-本研究的目的是评估一个表型细胞面板与肿瘤细胞从不同的患者和正常细胞的抗肿瘤疗效和毒性的抗癌药物的临床前配置文件。方法14种抗癌药物的抗肿瘤活性进行了测试，在超过100例实体或血液恶性肿瘤患者的肿瘤样本。针对四种正常细胞类型的药物活性用于评估正常组织毒性。在体外活性的药物进行了比较，由食品和药物管理局批准的适应症和建立不良事件profiles.Results在一般情况下，在体外药物活性的肿瘤细胞从患者反映已知的临床活性的药物研究。例如，伊马替尼在慢性髓性白血病中的临床活性在肿瘤组中被清楚地检测到。此外，根据临床使用，顺铂和硼替佐米分别在卵巢癌和骨髓瘤样品中显示出高活性。正常细胞模型大致反映了已知的临床毒性特征，并能够检测治疗指数的差异，例如。例如，在一个实施例中，靶向药物和传统细胞毒性药物之间的差异。例如，伊马替尼的高耐受性和众所周知的肾毒性cisplate.Conclusions在临床前药物开发，从患者的原发性肿瘤细胞可用于预测癌症诊断特异性活性，并可能有助于在选择诊断临床试验。通过一起使用肿瘤和毒性面板，可以导出关于治疗指数的信息，这在选择具有相似肿瘤效应的候选药物时可能是有用的。
Purpose The aim of this study was to evaluate a phenotypic cell panel with tumor cells from various patients and normal cells for preclinical profiles of antitumor efficacy and toxicity of anticancer drugs.Methods The antitumor activity of fourteen anticancer drugs was tested in over one hundred tumor samples from patients with solid or hematological malignancies. Drug activity against four normal cell types was used for the assessment of normal tissue toxicity. In vitro activity of the drugs was compared with indications approved by the Food and Drug Administration and established adverse event profiles.Results In general, in vitro drug activity in tumor cells from patients reflected known clinical activity of the drugs investigated. For example, the clinical activity of imatinib in chronic myeloid leukemia was clearly detected in the tumor panel. Further, and in accordance with clinical use, cisplatin and bortezomib showed high activity in ovarian cancer and myeloma samples, respectively. The normal cell models roughly reflected known clinical toxicity profiles and were able to detect differences in therapeutic index, e. g., between targeted drugs and classical cytotoxic agents. For example, the high tolerability of imatinib and the well-known renal toxicity of cisplatin were demonstrated.Conclusions In preclinical drug development, primary tumor cells from patients can be used for the prediction of cancer diagnosis-specific activity and may aid in the selection of diagnoses for clinical trials. By using tumor and toxicity panels together, information about therapeutic index may be derived, which may be useful when choosing among drug candidates with similar tumor effects.