title: Future paradigms for precision oncology.
abstract: Research has exposed cancer to be a heterogeneous disease with a high degree of inter-tumoral and intra-tumoral variability. Individual tumors have unique profiles, and these molecular signatures make the use of traditional histology-based treatments problematic. The conventional diagnostic categories, while necessary for care, thwart the use of molecular information for treatment as molecular characteristics cross tissue types.This is compounded by the struggle to keep abreast the scientific advances made in all fields of science, and by the enormous challenge to organize, cross-reference, and apply molecular data for patient benefit. In order to supplement the site-specific, histology-driven diagnosis with genomic, proteomic and metabolomics information, a paradigm shift in diagnosis and treatment of patients is required.While most physicians are open and keen to use the emerging data for therapy, even those versed in molecular therapeutics are overwhelmed with the amount of available data. It is not surprising that even though The Human Genome Project was completed thirteen years ago, our patients have not benefited from the information. Physicians cannot, and should not be asked to process the gigabytes of genomic and proteomic information on their own in order to provide patients with safe therapies. The following consensus summary identifies the needed for practice changes, proposes potential solutions to the present crisis of informational overload, suggests ways of providing physicians with the tools necessary for interpreting patient specific molecular profiles, and facilitates the implementation of quantitative precision medicine. It also provides two case studies where this approach has been used.
authors.affiliation: Department of Pediatric Hematology/Oncology, Floating Hospital for Children at Tufts Medical Center, Boston, MA, USA.|Department of Cell, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA, USA.
authors.forename: Giannoula Lakka
authors.initials: GL
authors.lastname: Klement
authors.affiliation: Department of Pathology, Tufts Medical Center, Boston, MA, USA.
authors.forename: Knarik
authors.initials: K
authors.lastname: Arkun
authors.affiliation: Department of Paediatric Oncology, University Hospital Brno, Brno, Czech Republic.|Regional Center for Applied Molecular Biology, RECAMO, Brno, Czech Republic.
authors.forename: Dalibor
authors.initials: D
authors.lastname: Valik
authors.affiliation: Department of Pediatric Hematology/Oncology, Floating Hospital for Children at Tufts Medical Center, Boston, MA, USA.
authors.forename: Tina
authors.initials: T
authors.lastname: Roffidal
authors.affiliation: CSTS Health Care®, Toronto, Canada.
authors.forename: Ali
authors.initials: A
authors.lastname: Hashemi
authors.affiliation: CSTS Health Care®, Toronto, Canada.
authors.forename: Christos
authors.initials: C
authors.lastname: Klement
authors.affiliation: CSTS Health Care®, Toronto, Canada.
authors.forename: Paolo
authors.initials: P
authors.lastname: Carmassi
authors.affiliation: CSTS Health Care®, Toronto, Canada.|Computer Science Department, University of Massachusetts, Amherst, MA, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Rietman
authors.affiliation: Department of Paediatric Oncology, University Hospital Brno, Brno, Czech Republic.|Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Slaby
authors.affiliation: Department of Paediatric Oncology, University Hospital Brno, Brno, Czech Republic.|Regional Center for Applied Molecular Biology, RECAMO, Brno, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Mazanek
authors.affiliation: Department of Paediatric Oncology, University Hospital Brno, Brno, Czech Republic.|Regional Center for Applied Molecular Biology, RECAMO, Brno, Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Mudry
authors.affiliation: 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Gabor
authors.initials: G
authors.lastname: Kovacs
authors.affiliation: Department of Pediatric Hematology-Oncology, Institute of Pediatrics, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Csongor
authors.initials: C
authors.lastname: Kiss
authors.affiliation: Antwerp University Hospital, Edegem, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Norga
authors.affiliation: Specialized Children's Oncohematology Hospital, Sofia, Bulgaria.
authors.forename: Dobrin
authors.initials: D
authors.lastname: Konstantinov
authors.affiliation: Department of Pediatric Hematology and Oncology, AP-HM, Marseille, France.|UMR S_911 CRO2 Aix Marseille Université, Marseille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: André
authors.affiliation: Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
authors.forename: Irene
authors.initials: I
authors.lastname: Slavc
authors.affiliation: Department of Pediatric Oncology, Emma Children Hospital Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Henk
authors.initials: H
authors.lastname: van Den Berg
authors.affiliation: Department of Pediatric Oncology, Comenius University, Bratislava, Slovakia.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kolenova
authors.affiliation: Department of Pathology, University Hospital Brno, Brno, Czech Republic.|Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Leos
authors.initials: L
authors.lastname: Kren
authors.affiliation: Faculty of Medicine, Masaryk University, Brno, Czech Republic.|Department of Pediatric Surgery, University Hospital Brno, Brno, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Tuma
authors.affiliation: Central European Institute of Technology, Masaryk University, Brno, Czech Republic.|Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Jarmila
authors.initials: J
authors.lastname: Skotakova
authors.affiliation: Department of Paediatric Oncology, University Hospital Brno, Brno, Czech Republic.|Faculty of Medicine, Masaryk University, Brno, Czech Republic.|ICRC St. Anna University Hospital Brno, Brno, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Sterba
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D008297:Male; D008495:Medical Oncology; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics; D057285:Precision Medicine; D012107:Research Design
keywords: genomics; metronomic chemotherapy; precision medicine; targeted therapy