Drug development and novel combination strategies with phytochemicals for precision medicine in cancer

Abstract

Precision medicine refers to matching the most accurate and effective treatment to each individual, and has the potential to manage diseases. In cancer, however, developing drug candidates and finding effective combination strategies are in great demand. Here, we present a framework covering drug development against a specific oncoprotein, effective combinations of drug and natural compounds, and a physiologically-achievable chemoprevention strategy. First, HI-B1 is synthesized and identified as a direct β-catenin inhibitor. A colon cancer patient-derived xenograft (PDX) model with a high level of β-catenin is sensitive to HI-B1. Second, a combination of aspirin with a ginger extract shows synergistic effect. Combining a ginger extract with aspirin treatment can significantly reduce the effective dose of aspirin while retaining its therapeutic effects in PDX mouse models. Third, multiple phytochemicals at low doses accumulatively inhibit one key protein to exert their chemopreventive and therapeutic effects. Natural ERK2 inhibitors are discovered using chemoinformatics, crystallography, cell biology and biochemistry. Each outcome could be used in a precision oncology workflow to help prevent and treat cancer efficiently.