Znati Sami, Carter Rebecca, Vasquez Marcos, Westhorpe Adam, Shahbakhti Hassan, Prince Jessica, Vlckova Petra, De Vellis Chiara, Bascal Zainab, Loizidou Marilena, Sharma Ricky A
University College London Cancer Institute, University College London, London WC1E 6BT, UK.
Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK.
Cancers (Basel). 2020 Jul 13;12(7):1878. doi: 10.3390/cancers12071878.
Hepatocellular Carcinoma (HCC) is increasing in incidence worldwide and requires new approaches to therapy. The combination of anti-angiogenic drug therapy and radiotherapy is one promising new approach. The anti-angiogenic drug vandetanib is a tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) and RET proto-oncogene with radio-enhancement potential. To explore the benefit of combined vandetanib and radiotherapy treatment for HCC, we studied outcomes following combined treatment in pre-clinical models.
Vandetanib and radiation treatment were combined in HCC cell lines grown and . In addition to 2D migration and clonogenic assays, the combination was studied in 3D spheroids and a syngeneic mouse model of HCC.
Vandetanib IC 50 s were measured in 20 cell lines and the drug was found to significantly enhance radiation cell kill and to inhibit both cell migration and invasion . , combination therapy significantly reduced cancer growth and improved overall survival, an effect that persisted for the duration of vandetanib treatment.
In 2D and 3D studies and in a syngeneic model , the combination of vandetanib plus radiotherapy was more efficacious than either treatment alone. This new combination therapy for HCC merits evaluation in clinical trials.
肝细胞癌（HCC）在全球范围内的发病率正在上升，需要新的治疗方法。抗血管生成药物治疗与放射治疗相结合是一种有前景的新方法。抗血管生成药物凡德他尼是一种血管内皮生长因子受体-2（VEGFR-2）和RET原癌基因的酪氨酸激酶抑制剂，具有放射增敏潜力。为了探索凡德他尼与放射治疗联合治疗HCC的益处，我们在临床前模型中研究了联合治疗后的结果。
将凡德他尼与放射治疗应用于培养的HCC细胞系。除了二维迁移和克隆形成试验外，还在三维球体和HCC同基因小鼠模型中研究了这种联合治疗。
在20个细胞系中测量了凡德他尼的半数抑制浓度（IC50），发现该药物能显著增强放射对细胞的杀伤作用，并抑制细胞迁移和侵袭。联合治疗显著降低了肿瘤生长并提高了总生存率，这种效果在凡德他尼治疗期间一直持续。
在二维和三维研究以及同基因模型中，凡德他尼联合放射治疗比单独的任何一种治疗都更有效。这种HCC新联合治疗方法值得在临床试验中进行评估。
