De Luise Monica, Kurelac Ivana, Coluccelli Sara, De Leo Antonio, Bartoszek Ewelina M, Iorio Maria, Grillini Marco, Coadă Camelia Alexandra, de Biase Dario, Marchio Lorena, López Mónica Núñez, Rimmer Natalie, Perrone Anna Myriam, De Iaco Pierandrea, Porcelli Anna Maria, Heinzelmann Viola, Martin Ivan, Jacob Francis, Muraro Manuele Giuseppe, Gasparre Giuseppe
Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
Centre for Applied Biomedical Research, University of Bologna, Bologna, Italy.
NPJ Precis Oncol. 2025 May 23;9(1):152. doi: 10.1038/s41698-025-00941-6.
Ovarian cancer (OC) poses significant treatment challenges due to late-stage diagnosis and a complex tumor microenvironment contributing to therapy resistance. We optimized a U-CUP perfusion-based bioreactor method to culture patient-derived primary and metastatic OC specimens, demonstrating that perfusion better preserves cancer cell viability and proliferation, both when fresh and slow-frozen tissues were used. Perfused cultures maintained key microenvironment components, including cancer-associated fibroblasts, endothelial and immune cells. Genetic analysis confirmed the retention in culture of tumor-specific driver mutations. We hence challenged ad hoc generated cisplatin-sensitive and resistant OC cells with cisplatin during growth in U-CUP, validating our system for the testing of drug response. Finally, treatment of slow-frozen OC tissues with carboplatin/paclitaxel revealed different degrees of response to treatment, as indicated by variations in tumor necrosis and number of residual PAX8 cells, providing the bases for the prompt evaluation of OC standard chemotherapy efficacy in our ex vivo system.
卵巢癌（OC）由于诊断时已处于晚期以及复杂的肿瘤微环境导致治疗耐药性，给治疗带来了重大挑战。我们优化了一种基于U-CUP灌注的生物反应器方法，用于培养患者来源的原发性和转移性OC标本，结果表明，无论是使用新鲜组织还是慢速冷冻组织，灌注都能更好地保持癌细胞的活力和增殖。灌注培养物保留了关键的微环境成分，包括癌症相关成纤维细胞、内皮细胞和免疫细胞。基因分析证实了肿瘤特异性驱动突变在培养中的保留。因此，我们在U-CUP中培养时，用顺铂对临时生成的顺铂敏感和耐药OC细胞进行了挑战，验证了我们用于测试药物反应的系统。最后，用卡铂/紫杉醇治疗慢速冷冻的OC组织，结果显示出不同程度的治疗反应，这通过肿瘤坏死和残余PAX8细胞数量的变化得以体现，为在我们的体外系统中快速评估OC标准化疗疗效提供了依据。
