Equipe Labellisée Ligue Contre le Cancer, Université de Poitiers, UMR CNRS 7285, Institut de Chimie des Milieux et Matériaux de Poitiers (IC2MP), 4 rue Michel-Brunet, TSA 51106, 86073 Poitiers, Cedex 9, France.
CHU de Poitiers, 86021 Poitiers, France.
Mol Pharm. 2023 Sep 4;20(9):4537-4545. doi: 10.1021/acs.molpharmaceut.3c00224. Epub 2023 Aug 14.
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 (), and a β-glucuronidase-responsive albumin-binding prodrug of monomethyl auristatin E (), 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 and currently used to treat patients with this pathology. The increased anticancer efficacy is due to either a synergistic or an additive effect between and selectively released from the glucuronide prodrug in the tumor microenvironment. Since numerous drug delivery systems such as antibody-drug conjugates employ as a cytotoxic payload, this finding may be of great interest for improving their therapeutic index by combining them with , particularly for the therapy of colorectal cancer.
在癌症治疗中，设计能够选择性地破坏肿瘤细胞而不损伤健康组织的创新治疗策略仍然极具挑战性。在这里，我们表明，两种靶向治疗的联合应用，包括贝伐珠单抗（）和单甲基奥瑞他汀 E 的β-葡糖苷酸响应性白蛋白结合前药（），对于治疗植入小鼠的结直肠癌是有效的。这种联合治疗产生的治疗活性优于目前用于治疗该病理患者的联合用药。抗癌效果的增强是由于在肿瘤微环境中从葡糖苷酸前药中选择性释放的 和 之间的协同或相加作用。由于许多药物递送系统，如抗体药物偶联物，将 用作细胞毒性有效载荷，因此这一发现对于通过与 联合使用来提高其治疗指数可能具有重要意义，特别是对于结直肠癌的治疗。
