Tonra James R, Prewett Marie, Corcoran Erik, Hicklin Daniel J, Zhu Zhenping
ImClone Systems Inc, New York, NY, USA.
Methods Mol Biol. 2009;525:545-57, xv. doi: 10.1007/978-1-59745-554-1_30.
Targeted therapy for cancer is shifting towards an approach of inhibiting multiple pathways, justified in part by the ability of cancer cells to overcome the inhibition of a single pathway. However the literature is replete with preclinical data supporting the anticancer potential of numerous combinations of targeted agents, making it difficult to select the combination strategies to invest in through clinical development. One characteristic of a combination strategy that can be utilized for prioritization is synergy. Synergy indicates that the effect of the combination is greater than that predicted from the monotherapy potencies. Here we describe a detailed method for establishing synergy between two treatments in vivo. We utilized this method to establish that antibodies targeting the epidermal growth factor receptor and vascular endothelial growth factor receptor-2 are synergistic with regard to antitumor effects, in a BxPC-3 subcutaneous xenograft model for pancreatic cancer.
癌症的靶向治疗正朝着抑制多种信号通路的方法转变，部分原因在于癌细胞能够克服单一信号通路的抑制作用。然而，文献中充斥着支持多种靶向药物组合具有抗癌潜力的临床前数据，这使得难以选择通过临床开发进行投资的联合策略。可用于确定优先级的联合策略的一个特征是协同作用。协同作用表明联合治疗的效果大于单药效力所预测的效果。在这里，我们描述了一种在体内确定两种治疗方法之间协同作用的详细方法。我们利用这种方法确定，在胰腺癌的BxPC-3皮下异种移植模型中，靶向表皮生长因子受体和血管内皮生长因子受体-2的抗体在抗肿瘤作用方面具有协同作用。
