N.N. Blokhin National Medical Research Center of Oncology, 115478 Moscow, Russia.
Faculty of Medicine, Sechenov University, 119991 Moscow, Russia.
Int J Mol Sci. 2023 Jul 31;24(15):12292. doi: 10.3390/ijms241512292.
Treatment of highly malignant soft tissue sarcomas (STSs) requires multicomponent therapy including surgery, radiotherapy, and chemotherapy. Despite the advancements in targeted cancer therapies, cytostatic drug combinations remain the gold standard for STS chemotherapy. The lack of algorithms for personalized selection of STS chemotherapy leads to unhelpful treatment of chemoresistant tumors, causing severe side effects in patients. The goal of our study is to assess the applicability of in vitro chemosensitivity/resistance assays (CSRAs) in predicting STS chemoresistance. Primary cell cultures were obtained from 148 surgery samples using enzymatic and mechanical disaggregation. CSRA was performed using resazurin-based metabolic activity measurement in cells cultured with doxorubicin, ifosfamide, their combination and docetaxel, gemcitabine, and also their combination for 7 days. Both the clinical data of patients and the CSRA results demonstrated a higher resistance of some cancer histotypes to specific drugs and their combinations. The correlation between the CSRA results for doxorubicin and ifosfamide and clinical responses to the combination chemotherapy with these drugs was demonstrated via Spearman rank order correlation. Statistically significant differences in recurrence-free survival were also shown for the groups of patients formed, according to the CSRA results. Thus, CSRAs may help both practicing physicians to avoid harmful and useless treatment, and researchers to study new resistance markers and to develop new STS drugs.
治疗高度恶性软组织肉瘤(STS)需要多组分治疗,包括手术、放疗和化疗。尽管靶向癌症治疗取得了进展,但细胞抑制药物联合仍是 STS 化疗的金标准。缺乏 STS 化疗的个性化选择算法导致对耐药肿瘤的无益治疗,导致患者出现严重的副作用。我们的研究目的是评估体外化疗敏感性/耐药性测定(CSRAs)在预测 STS 化疗耐药性中的适用性。使用酶和机械分散从 148 个手术样本中获得原代细胞培养物。使用基于 Resazurin 的代谢活性测量法,在培养有阿霉素、异环磷酰胺、两者联合以及多西他赛、吉西他滨、两者联合的细胞中进行 CSRA,培养 7 天。患者的临床数据和 CSRA 结果均表明,某些癌症组织型对特定药物及其组合的耐药性更高。通过 Spearman 等级相关分析,证明了 CSRA 对阿霉素和异环磷酰胺的结果与对这些药物联合化疗的临床反应之间的相关性。还根据 CSRA 结果显示了无复发生存率的统计学显著差异。因此,CSRAs 不仅可以帮助临床医生避免有害和无效的治疗,还可以帮助研究人员研究新的耐药标志物并开发新的 STS 药物。