Hoffmann Oliver Ingo, Regenauer Manuel, Czogalla Bastian, Brambs Christine, Burges Alexander, Mayer Barbara
SpheroTec GmbH, Am Klopferspitz 19, 82152 Martinsried, Germany.
Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Munich, Marchioninistraße 15, 81377 Munich, Germany.
Cancers (Basel). 2022 May 3;14(9):2279. doi: 10.3390/cancers14092279.
Recurrent ovarian-cancer patients face low 5-year survival rates despite chemotherapy. A variety of guideline-recommended second-line therapies are available, but they frequently result in trial-and-error treatment. Alterations and adjustments are common in the treatment of recurrent ovarian cancer. The drug response of 30 lesions obtained from 22 relapsed ovarian cancer patients to different chemotherapeutic and molecular agents was analyzed with the patient-derived ovarian-cancer spheroid model. The profile of druggable biomarkers was immunohistochemically assessed. The second-line combination therapy of carboplatin with gemcitabine was significantly superior to the combination of carboplatin with PEGylated liposomal doxorubicin (p < 0.0001) or paclitaxel (p = 0.0007). Except for treosulfan, all nonplatinum treatments tested showed a lesser effect on tumor spheroids compared to that of platinum-based therapies. Treosulfan showed the highest efficacy of all nonplatinum agents, with significant advantage over vinorelbine (p < 0.0001) and topotecan (p < 0.0001), the next best agents. The comparative testing of a variety of treatment options in the ovarian-cancer spheroid model resulted in the identification of more effective regimens for 30% of patients compared to guideline-recommended therapies. Recurrent cancers obtained from different patients revealed profound interpatient heterogeneity in the expression pattern of druggable protein biomarkers. In contrast, different lesions obtained from the same patient revealed a similar drug response and biomarker expression profile. Biological heterogeneity observed in recurrent ovarian cancers might explain the strong differences in the clinical drug response of these patients. Preclinical drug testing and biomarker profiling in the ovarian-cancer spheroid model might help in optimizing treatment management for individual patients.
尽管接受了化疗，复发性卵巢癌患者的5年生存率仍然很低。有多种指南推荐的二线治疗方法可供选择，但它们常常导致反复试验性治疗。复发性卵巢癌的治疗中改变和调整很常见。利用患者来源的卵巢癌球体模型分析了22例复发性卵巢癌患者的30个病灶对不同化疗药物和分子药物的反应。通过免疫组织化学评估了可成药生物标志物的特征。卡铂与吉西他滨的二线联合治疗显著优于卡铂与聚乙二醇化脂质体阿霉素的联合治疗（p<0.0001）或卡铂与紫杉醇的联合治疗（p=0.0007）。除了苏消安，所有测试的非铂类治疗与铂类治疗相比，对肿瘤球体的作用较小。苏消安在所有非铂类药物中显示出最高的疗效，与其次有效的药物长春瑞滨（p<0.0001）和拓扑替康（p<0.0001）相比具有显著优势。在卵巢癌球体模型中对多种治疗方案进行比较测试，结果表明，与指南推荐的治疗方法相比，30%的患者可确定更有效的治疗方案。从不同患者获得的复发性癌症在可成药蛋白生物标志物的表达模式上显示出患者间的显著异质性。相比之下，从同一患者获得的不同病灶显示出相似的药物反应和生物标志物表达谱。复发性卵巢癌中观察到的生物学异质性可能解释了这些患者临床药物反应的巨大差异。在卵巢癌球体模型中进行临床前药物测试和生物标志物分析可能有助于优化个体患者的治疗管理。
