肿瘤干细胞试验治疗铂耐药复发性卵巢癌。

Candace M Howard, Stephen Bush, Nadim Bou Zgheib, Seth T Lirette, Antonio Cortese, Antonio Mollo, Jagan Valluri, Pier Paolo Claudio
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引用次数: 3

摘要

背景:癌症的疾病复发和进展是一种常见的事件,伴随着铂耐药性或难治性疾病的发展。耐药癌症干细胞(CSCs)的存在有助于这种难以治疗的疾病的肿瘤传播、维持和治疗耐药性。我们开发了ChemoID,这是一种针对CSC的细胞毒性协同试验,通过使用新鲜癌症活组织检查,从一组FDA批准的化疗中确定最有效的化疗治疗。患者和方法:根据医师指示,从连续78例癌症3期复发患者中收集腹水或介入放射学活组织检查。在可能的情况下,使用该测定的测试结果来治疗使用最高细胞杀伤药物的患者,考虑到他们的健康状况,并在需要时减少剂量。对CT和PET扫描进行图表分析和回顾以确定患者的肿瘤反应、无进展生存期(PFS)和无进展生存率(PFS)的结果,结果:我们观察到,与历史中位PFS和OS相比,和/或与不能接受高细胞杀伤化疗的患者相比,接受CSCs药物反应分析指导的高级细胞杀伤化疗剂治疗的复发性卵巢癌症患者的中位PFS或OS有所改善(PFS低细胞杀伤3.5个月对高细胞杀伤12.0个月;OS低细胞杀伤6.0个月对高细胞杀伤15.0个月)。结论:该数据表明,当一线治疗失败时,以及当有多种临床可接受和等效的治疗可用时,针对CSCs的药物细胞毒性测定可能是优化治疗选择的有用工具。
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Cancer Stem Cell Assay for the Treatment of Platinum-Resistant Recurrent Ovarian Cancer.

Background: Disease recurrence and progression of ovarian cancer is a common event, which is accompanied by the development of platinum-resistant or refractory disease. The presence of chemo-resistant Cancer Stem Cells (CSCs) contribute to tumor propagation, maintenance, and treatment resistance of this difficult to treat disease. We have developed ChemoID, a cytotoxic synergy assay against CSCs that identifies the most effective chemotherapy treatment from a panel of FDA-approved chemotherapies using fresh cancer biopsies.

Patients and methods: Ascites or interventional radiology biopsies were collected under physician order from 78 consecutive patients affected by 3rd relapsed ovarian cancer. Test results from the assay were used when possible to treat patients with the highest cell kill drugs, taking into consideration their health status and using dose reductions, if needed. A chart analysis and review of CT and PET scans were performed to determine patients' outcomes for tumor response, Progression-Free Survival (PFS), and Overall Survival (OS).

Results: We observed that recurrent ovarian cancer patients treated with high-cell kill chemotherapy agents guided by the CSCs drug response assay had an improvement in their median PFS and OS when compared to historical median PFS and OS and/or when compared to patients who could not receive high cell kill chemotherapies (PFS low cell kill 3.5 months vs. high cell kill 12.0 months; OS low cell kill 6.0 months vs. high cell kill 15.0 months).

Conclusion: This data indicates that the drug cytotoxicity assay aimed at targeting CSCs may be a useful tool for optimizing treatment selection when first-line therapy fails, and when there are multiple clinically-acceptable and -equivalent treatments available.

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