Combination of Targeted Therapies for Colorectal Cancer Treatment.

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.