Abstract
Drug combination is a critically important therapeutic approach for complex diseases such as cancer and HIV due to its potential for efficacy at lower, less toxic doses and the need to move new therapies rapidly into clinical trials. One of the key issues is to identify which combinations are additive, synergistic, or antagonistic. While the value of multidrug combinations has been well recognized in the cancer research community, to our best knowledge, all existing experimental studies rely on fixing the dose of one drug to reduce the dimensionality, e.g. looking at pairwise two-drug combinations, a suboptimal design. Hence, there is an urgent need to develop experimental design and analysis methods for studying multidrug combinations directly. Because the complexity of the problem increases exponentially with the number of constituent drugs, there has been little progress in the development of methods for the design and analysis of high-dimensional drug combinations. In fact, contrary to common mathematical reasoning, the case of three-drug combinations is fundamentally more difficult than two-drug combinations. Apparently, finding doses of the combination, number of combinations, and replicates needed to detect departures fr...Continue Reading
References
Oct 1, 1990·Antiviral Research·M N Prichard, C Shipman
Jan 1, 1990·Antiviral Research·J Sühnel
Dec 1, 1983·The Journal of Antimicrobial Chemotherapy·M C BerenbaumT P Felegie
Mar 8, 1996·Biochemical Pharmacology·J J Martinez-IrujoE Santiago
Aug 22, 2000·Antimicrobial Agents and Chemotherapy·D A Stevens
Jun 24, 2003·Statistics in Medicine·Ming TanPeter J Houghton
Sep 27, 2003·Leukemia·X-Y PeiS Grant
Aug 22, 2006·Nature Chemical Biology·Jonathan B FitzgeraldPeter K Sorger
Dec 13, 2006·Biometrics·Maiying Kong, J Jack Lee
Jan 12, 2008·Statistics in Medicine·Hong-Bin FangMing Tan
Sep 6, 2008·Science·Siân JonesKenneth W Kinzler
Oct 22, 2008·Nature Chemical Biology·Andrew L Hopkins
Feb 12, 2009·Cancer Research·William N Hait, Trevor W Hambley
Feb 12, 2009·Cancer Research·Trevor W Hambley, William N Hait
Feb 19, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ken ShiozawaDouglas D Ross
Dec 29, 2009·Statistics in Biopharmaceutical Research·J Jack Lee, Maiying Kong
Feb 26, 2010·Journal of Biopharmaceutical Statistics·Hong-Bin FangMing Tan
Apr 9, 2010·The New England Journal of Medicine·Joao B Xavier, Chris Sander
Mar 29, 2013·Asian Pacific Journal of Cancer Prevention : APJCP·Suleyman AliciUNKNOWN Anatolian Society of Medical Oncology
Citations
Sep 30, 2017·Biometrics·Hengzhen HuangMing T Tan
Apr 10, 2019·Endocrine-related Cancer·Robert ClarkeYue Wang
Sep 25, 2019·Current Drug Targets·Kening LiDong-Qing Wei
Aug 8, 2019·BMC Bioinformatics·Geonhee LeeJaegyoon Ahn
Dec 19, 2019·Frontiers in Pharmacology·Simone LedererTom Heskes
Dec 2, 2015·Nature Methods·John C Ashton