Urquhart Aaron J, Glass Christian H, Humphries Tyrone L R, Kassianos Andrew J, Vesey David A, Wood Simon T, Gobe Glenda C, Ellis Robert J
Princess Alexandra Hospital, Metro South Hospital and Health Service, Brisbane, QLD, Australia.
Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
Per Med. 2025 Apr;22(2):83-91. doi: 10.1080/17410541.2025.2473303. Epub 2025 Mar 3.
Metastatic renal cell carcinoma (RCC) is often treated with a combination of immunotherapy and tyrosine kinase inhibitors (TKIs). Patient-derived RCC cells were cultured and inter-individual differences to treatment with a panel of TKIs were evaluated.
Tumor tissue was collected during nephrectomy. Cells were cultured and treated with a panel of clinically relevant TKIs (sunitinib, cabozantinib, pazopanib, axitinib) at concentrations of 5 µM for 48-72 hours. Cell viability was evaluated using MTT assays. One-sided T-tests were used to evaluate results.
Patient-derived cancer cells were able to be grown beyond 10 passages from 12/38 samples collected (27%). Four patient-derived samples were tested against the TKI panel. No substantial difference between drugs was seen for two samples. In one sample, there was a clear superior response to sunitinib (48% mean viability, vs >75% for the other drugs). For the final sample, sunitinib, cabozantinib, and axitinib demonstrated a superior response compared with pazopanib (71%, 77%, 70%, and 85% mean viability, respectively).
Inter-individual variability in the responses of patient-derived RCC cultures to TKIs was seen, which may have biological and clinical significance. Future directions could build on this work to develop personalized cancer susceptibility profiles, with potential for translation into a clinical trial.
转移性肾细胞癌（RCC）通常采用免疫疗法和酪氨酸激酶抑制剂（TKIs）联合治疗。培养患者来源的肾癌细胞，并评估其对一组TKIs治疗的个体差异。
在肾切除术中收集肿瘤组织。培养细胞并用一组临床相关的TKIs（舒尼替尼、卡博替尼、帕唑帕尼、阿昔替尼）以5µM的浓度处理48 - 72小时。使用MTT法评估细胞活力。采用单侧t检验评估结果。
从收集的38个样本中的12个（27%）获得的患者来源的癌细胞能够传代超过10代。对4个患者来源的样本进行了TKIs检测。两个样本在药物之间未观察到显著差异。在一个样本中，对舒尼替尼有明显更好（更优）的反应（平均活力48%，而其他药物>75%）。对于最后一个样本，与帕唑帕尼相比，舒尼替尼、卡博替尼和阿昔替尼表现出更好（更优）的反应（平均活力分别为71%、77%、70%和85%）。
观察到患者来源的肾癌细胞培养物对TKIs的反应存在个体差异，这可能具有生物学和临床意义。未来的研究方向可以基于这项工作来开发个性化的癌症易感性概况，并有可能转化为临床试验。
