Effects of Dual Targeted Therapies of Anticancer Drugs in Preclinical Models of Colorectal Cancer

Colorectal cancer kills over 50,000 people per year in the United States. While individual drugs can be somewhat effective, the median survival remains only 25-28 months. New therapies are needed, and dual targeted inhibitors are a promising area. A total of 7 cell lines, 4 of which are presented, were treated in varying concentrations of TAK228, an mTORC1/2 inhibitor, and trametinib, a MEK1/2 inhibitor Proliferation, apoptosis, and viability assays as well as immunoblotting were performed to determine the mechanism and efficacy. Immunoblotting determined that the target of TAK228 is mTORC1/2 and that Survivin may be a mechanism for the anti-proliferative effects. The study indicates that TAK228 and trametinib are viable combination partners for the possible future treatment of PI3K mutated cancers, especially within the RAS-mutant area