title: Prediction of multidimensional drug dose responses based on measurements of drug pairs.
abstract: Finding potent multidrug combinations against cancer and infections is a pressing therapeutic challenge; however, screening all combinations is difficult because the number of experiments grows exponentially with the number of drugs and doses. To address this, we present a mathematical model that predicts the effects of three or more antibiotics or anticancer drugs at all doses based only on measurements of drug pairs at a few doses, without need for mechanistic information. The model provides accurate predictions on available data for antibiotic combinations, and on experiments presented here on the response matrix of three cancer drugs at eight doses per drug. This approach offers a way to search for effective multidrug combinations using a small number of experiments.
authors: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors: Anat
authors: A
authors: Zimmer
authors: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors: Itay
authors: I
authors: Katzir
authors: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors: Erez
authors: E
authors: Dekel
authors: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors: Avraham E
authors: 0000-0002-4479-3423
authors: AE
authors: Mayo
authors: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel uri.alon@weizmann.ac.il.
authors: Uri
authors: U
authors: Alon
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D006801:Humans; D008962:Models, Theoretical; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents
keywords: cancer treatment; drug cocktails; drug combinations; mechanism-free formula; predictive formula