title: Two is better than one; toward a rational design of combinatorial therapy.
abstract: Drug combination is an appealing strategy for combating the heterogeneity of tumors and evolution of drug resistance. However, the rationale underlying combinatorial therapy is often not well established due to lack of understandings of the specific pathways responding to the drugs, and their temporal dynamics following each treatment. Here we present several emerging trends in harnessing properties of biological systems for the optimal design of drug combinations, including the type of drugs, specific concentration, sequence of addition and the temporal schedule of treatments. We highlight recent studies showing different approaches for efficient design of drug combinations including single-cell signaling dynamics, adaption and pathway crosstalk. Finally, we discuss novel and feasible approaches that can facilitate the optimal design of combinatorial therapy.
authors: Department of Systems Biology, Harvard Medical School, Boston, MA, United States.
authors: Sheng-Hong
authors: SH
authors: Chen
authors: Department of Systems Biology, Harvard Medical School, Boston, MA, United States. Electronic address: galit_lahav@hms.harvard.edu.
authors: Galit
authors: G
authors: Lahav
mesh_terms: D004338:Drug Combinations; D015195:Drug Design; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004338:Drug Combinations