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

Abstract

<p>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.</p>