Targeting KRAS mutant colorectal cancer by inducing a cytotoxic oxidative stress

Collaborative Research Program 2021-2023

We developed a novel oxidative drug combination of ATO and D-VC that is highly effective in targeting KRAS mutant colorectal cancer cells manifested by a potent cytotoxic impact in cell culture and suppression of tumor growth in xenograft models. Considering that both components ATO and D-VC of the developed drug combination are the Food and Drug Administration (FDA) approved compounds, the main purpose of this grant application is to determine efficacy of the ATO/D-VC combination in suppressing KRAS mutant colorectal human cancers. To address the main purpose of this grant application, we will study the following three Specific Aims: To determine how the ATO/D-VC drug combination leads to a cytotoxic generation of ROS in KRAS mutant colorectal cancer cells (Aim 1); To define the types of human KRAS mutant colorectal cancers sensitive to the oxidative ATO/D-VC drug combination (Aim 2); To determine the efficacy of ATO/D-VC drug combination in suppressing KRAS mutant colorectal cancers by performing the Phase I and II clinical trials. (Aim 3).