title: Formalizing an integrative, multidisciplinary cancer therapy discovery workflow.
abstract: Although many clinicians and researchers work to understand cancer, there has been limited success to effectively combine forces and collaborate over time, distance, data, and budget constraints. Here we present a workflow template for multidisciplinary cancer therapy that was developed during the 2nd Annual Workshop on Cancer Systems Biology sponsored by Tufts University, Boston, Massachusetts, in July 2012. The template was applied to the development of a metronomic therapy backbone for neuroblastoma. Three primary groups were identified: clinicians, biologists, and quantitative scientists (mathematicians, computer scientists, and engineers). The workflow described their integrative interactions; parallel or sequential processes; data sources and computational tools at different stages as well as the iterative nature of therapeutic development from clinical observations to in vitro, in vivo, and clinical trials. We found that theoreticians in dialog with experimentalists could develop calibrated and parameterized predictive models that inform and formalize sets of testable hypotheses, thus speeding up discovery and validation while reducing laboratory resources and costs. The developed template outlines an interdisciplinary collaboration workflow designed to systematically investigate the mechanistic underpinnings of a new therapy and validate that therapy to advance development and clinical acceptance.
authors: Authors' Affiliations: University of Texas Medical School at Houston, Houston, Texas; Center of Cancer Systems Biology, Steward Research & Specialty Projects Corp., St. Elizabeth's Medical Center, Tufts University School of Medicine; Division of Cell and Molecular Biology, Department of Biology, Boston University, Boston, Massachusetts; Department of Mathematics, Dartmouth College, Hanover, New Hampshire; St. Jude Children's Research Hospital, Memphis, Tennessee; Hospital for Sick Children, Toronto, Ontario, Canada; Children's Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Randwick, NSW, Australia; and Metronomics Global Health Initiative, Marseille, France.
authors: Mary F
authors: MF
authors: McGuire
authors: Heiko
authors: H
authors: Enderling
authors: Dorothy I
authors: DI
authors: Wallace
authors: Jaspreet
authors: J
authors: Batra
authors: Marie
authors: M
authors: Jordan
authors: Sushil
authors: S
authors: Kumar
authors: John C
authors: JC
authors: Panetta
authors: Eddy
authors: E
authors: Pasquier
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods; D019468:Disease Management; D006801:Humans; D008495:Medical Oncology / Q000379:methods / Q000458:organization & administration*; D009369:Neoplasms / Q000628:therapy*; D057188:Workflow
references: Pediatr Blood Cancer. 2012 Sep;59(3):511-7
references: 22147459
references: J Pediatr Hematol Oncol. 2011 Jan;33(1):25-30
references: 21063221
references: Pediatr Blood Cancer. 2014 Apr;61(4):636-42
references: 24123865
references: N Biotechnol. 2012 Sep 15;29(6):709-19
references: 22440585
references: Pharmacotherapy. 2010 Feb;30(2):177-94
references: 20099992
references: Nat Rev Clin Oncol. 2012 Apr 17;9(6):338-50
references: 22508028
references: Nat Rev Cancer. 2012 Jan 12;12(2):133-43
references: 22237392
references: J Mol Endocrinol. 2012 Mar 29;48(3):R31-43
references: 22355097
references: Clin Pharmacokinet. 2001;40(12):883-92
references: 11735607
references: EMBO J. 1997 Jun 2;16(11):2985-95
references: 9214616
references: Mol Cancer. 2010 Jul 12;9:185
references: 20624283
references: J Health Care Poor Underserved. 2010 Aug;21(3 Suppl):35-45
references: 20675944
references: Nat Rev Cancer. 2011 Feb;11(2):135-41
references: 21258397
references: Drug Discov Today. 2011 Feb;16(3-4):93-8
references: 21134487
references: J Clin Invest. 2005 Apr;115(4):795-7
references: 15841166
references: Eur J Pharmacol. 2009 Dec 25;625(1-3):108-21
references: 19825370
references: Exp Ther Med. 2010 Sep;1(5):739-746
references: 22993597
references: Paediatr Anaesth. 2011 Mar;21(3):214-21
references: 21244569
references: Cancer Res. 2013 May 15;73(10):2949-54
references: 23492368
references: Clin Cancer Res. 2008 Jan 1;14(1):318-25
references: 18172284
references: J Biomed Inform. 2012 Apr;45(2):372-87
references: 22200681
references: J Pharmacokinet Pharmacodyn. 2005 Apr;32(2):185-97
references: 16283534
references: Nature. 1987 Dec 3-9;330(6147):493-5
references: 3683563
references: Cancer Res. 1988 May 1;48(9):2432-9
references: 3356007
references: AMIA Annu Symp Proc. 2008 Nov 06;:566-70
references: 18998958
references: J Investig Med. 2011 Aug;59(6):893-903
references: 21712727
references: J Natl Cancer Inst. 1990 Jan 3;82(1):4-6
references: 1688381
references: Toxicol Lett. 2013 Jun 20;220(1):26-34
references: 23566899
references: Ann Clin Lab Sci. 2012 Summer;42(3):243-57
references: 22964612
references: Clin Cancer Res. 2012 Nov 1;18(21 Suppl):S1-100
references: 22977188
references: Clin Pharmacol Ther. 1997 Mar;61(3):275-91
references: 9084453
references: Cancer Epidemiol Biomarkers Prev. 2003 Aug;12(8):705-12
references: 12917200
references: Nat Rev Cancer. 2010 Mar;10(3):221-30
references: 20179714
references: CBE Life Sci Educ. 2010 Fall;9(3):316-22
references: 20810964
references: Nat Rev Clin Oncol. 2010 Aug;7(8):455-65
references: 20531380
references: Cancer Lett. 2005 Oct 18;228(1-2):195-201
references: 15975708
references: Int J Antimicrob Agents. 2008 Apr;31(4):369-74
references: 18215509
references: Clin Pharmacol Ther. 2011 Apr;89(4):487-8; author reply 488
references: 21326289
references: Br J Cancer. 2013 Jun 25;108(12):2485-94
references: 23695022
references: Clin Pharmacol Ther. 2010 Aug;88(2):166-82
references: 20613720
references: Curr Gene Ther. 2009 Oct;9(5):368-74
references: 19860651
references: J Pediatr Hematol Oncol. 2005 Nov;27(11):573-81
references: 16282886
references: J Clin Pharmacol. 2008 Feb;48(2):146-56
references: 18199891
references: Oncotarget. 2011 Dec;2(12):960-5
references: 22156656