iCTC drug resistance (CDR) Testing ex vivo for evaluation of available therapies to treat patients with epithelial ovarian cancer.
iCTC drug resistance (CDR) Testing ex vivo for evaluation of available therapies to treat patients with epithelial ovarian cancer.
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DOI：
10.1016/j.ygyno.2017.08.018
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发表时间：
2017-11
影响因子：
4.7
通讯作者：
M. Pearl;Huan Dong;Qiang Zhao;Shaun Tulley;Marlo K. Dombroff;Wen‐Tien Chen
中科院分区：
文献类型：
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作者：
M. Pearl;Huan Dong;Qiang Zhao;Shaun Tulley;Marlo K. Dombroff;Wen‐Tien Chen
目标上皮性卵巢癌（EOC）的管理可以使用侵袭性循环肿瘤细胞（iCTC）的系列测量来监测治疗反应并早期检测疾病进展/复发。本研究的目标是开发 iCTC 耐药性 (CDR) 测定，并评估患者来源的培养 iCTC 在选择可用疗法方面的临床意义。方法使用紫杉醇-卡铂和其他八种用于患者的浓度的 EOC 药物进行 CDR 测定。六名患者在初次紫杉醇-卡铂化疗前献血，一名复发患者，六名患者在化疗期间和化疗后，以及两名患有良性疾病的患者用于程序控制。 CDR 得分高于和低于 100 分别表示对该药物的敏感性和耐药性。结果 6 个治疗前样本中的 5 个样本具有 > 20 iCTC/>111 CDR 的紫杉醇-卡铂敏感性，1 个样本具有 40 iCTC/23 CDR 的耐药性。复发样本具有 58 个 iCTC/5 个 CDR 耐药性。六名治疗后患者中的四名 iCTC 降至 0/>153 CDR，表明敏感性，而两名患者的 iCTC > 45 / <85 CDR 表明耐药性。患者的治疗史和随访证实，当iCTC对紫杉醇-卡铂敏感时，患者处于缓解或缓解状态；当iCTC对紫杉醇-卡铂耐药时，患者处于复发或复发状态。结论有必要对CDR测定进行进一步研究，以检验其在治疗患者之前选择药物的用途。
GoalsManagement of epithelial ovarian cancer (EOC) could use serial measurements of invasive circulating tumor cells (iCTCs) for monitoring therapeutic response and early detection of disease progression/recurrence. Goals of this study are to develop an iCTC drug resistance (CDR) assay and to evaluate clinical significance of patient-derived, cultured iCTCs in selecting available therapies.MethodsThe CDR assay using Taxol-Carboplatin and eight other EOC drugs at the concentration used for patients was performed. Blood was donated by six patients before primary Taxol-Carboplatin chemotherapy, one recurrent patient, six patients during and after their course of chemotherapy, and two patients with benign disease for procedure control. CDR score above and below 100 indicates sensitivity and resistance, respectively, to that drug.ResultsFive of six pre-therapy samples had > 20 iCTCs/>111 CDR for Taxol-Carboplatin sensitivity, and one had 40 iCTCs/23 CDR for resistance. The recurrent sample had 58 iCTCs/5 CDR for resistance. Four of six post-therapy patients had iCTCs decreased to 0/>153 CDR indicating sensitivity, while two patients had > 45 iCTCs/<85 CDR indicating resistance. The patients' treatment history and follow-up confirmed that patients were in response or remission when iCTCs were sensitive to Taxol-Carboplatin, and patients were in relapse or recurrence when iCTCs were resistant to Taxol-Carboplatin.ConclusionFurther investigation on the CDR assay is warranted to examine its use in selecting drugs before treating a patient.