肿瘤病理治疗中，设计能够选择性破坏肿瘤细胞而保护健康组织的创新治疗策略仍然具有极高的挑战性。在本研究中，我们展示了两种靶向治疗方法的联合应用对移植至小鼠体内的结直肠癌的治疗是有效的。其中一种治疗方法是使用贝伐单抗(Bev)，另一种是使用β-葡萄糖醛酸酶响应型结合白蛋白的单甲基奥瑞斯汀E(MMAE)前药。与目前用于治疗该病的FOLFOX和Bev联合应用相比，这种联合治疗产生了更高的治疗活性。这种增强的抗癌效果是由于肿瘤微环境中由葡萄糖醛酸酶前药选择性释放出的Bev和MMAE之间的协同或加成效应。由于许多药物递送系统，如抗体药物偶联物，使用MMAE作为细胞毒素负荷，这一发现可能对于通过将其与Bev联合应用来改善治疗性指数，特别是用于治疗结直肠癌的治疗，具有极大的意义。

The design of innovative therapeutic strategies enabling the selective destruction of tumor cells while sparing healthy tissues remains highly challenging in cancer therapy. Here, we show that the combination of two targeted therapies, including bevacizumab (Bev), and a β-glucuronidase-responsive albumin-binding prodrug of monomethyl auristatin E (MMAE), is efficient for the treatment of colorectal cancer implanted in mice. This combined therapy produces a therapeutic activity superior to that of the association of FOLFOX and Bev currently used to treat patients with this pathology. The increased anticancer efficacy is due to either a synergistic or an additive effect between Bev and MMAE selectively released from the glucuronide prodrug in the tumor microenvironment. Since numerous drug delivery systems such as antibody-drug conjugates employ MMAE as a cytotoxic payload, this finding may be of great interest for improving their therapeutic index by combining them with Bev, particularly for the therapy of colorectal cancer.