Prospects on Strategies for Therapeutically Targeting Oncogenic Regulatory Factors by Small‐Molecule Agents

摘要: Although the Human Genome Project has raised much hope for identification of druggable genetic targets cancer and other diseases, this target-based approach not improved productivity in drug discovery over traditional approach. Analyses known human target proteins currently marketed drugs reveal that these only a limited number as compared to whole proteome. In contrast genome-based targets, mechanistic are derived from empirical research, at cellular or molecular levels, disease models and/or patients, thereby enabling exploration greater beyond genome epigenome. The paradigm shift made tremendous headway developing new therapeutic agents targeting different clinically relevant mechanisms/pathways cells. Prospects article, we provide an overview potential related following four emerging areas: (1) tumor metabolism (the Warburg effect), (2) dysregulated protein turnover (E3 ubiquitin ligases), (3) protein-protein interactions, (4) unique DNA high-order structures protein-DNA interactions. Nonetheless, considering phenotypic heterogeneities characterize cells, development resistance cells by adapting signaling circuitry take advantage redundant pathways feedback/crosstalk systems is possible. This "phenotypic adaptation" underlies rationale using combinations targeted with cytotoxic drugs.