title: Treatment Algorithms Based on Tumor Molecular Profiling: The Essence of Precision Medicine Trials.
abstract: With the advent of high-throughput molecular technologies, several precision medicine (PM) studies are currently ongoing that include molecular screening programs and PM clinical trials. Molecular profiling programs establish the molecular profile of patients' tumors with the aim to guide therapy based on identified molecular alterations. The aim of prospective PM clinical trials is to assess the clinical utility of tumor molecular profiling and to determine whether treatment selection based on molecular alterations produces superior outcomes compared with unselected treatment. These trials use treatment algorithms to assign patients to specific targeted therapies based on tumor molecular alterations. These algorithms should be governed by fixed rules to ensure standardization and reproducibility. Here, we summarize key molecular, biological, and technical criteria that, in our view, should be addressed when establishing treatment algorithms based on tumor molecular profiling for PM trials.
authors.affiliation: Affiliations of authors:Department of Medical Oncology, Institut Curie , Paris & Saint-Cloud , France (CLT, MK, MA); EA7285 Versailles-St-Quentin-en-Yvelines University , France (CLT, RR); Investigational Cancer Therapeutics, M. D. Anderson Cancer Center , Houston, TX (AMT); Drug Development Program, Department of Medical Oncology and Hematology, Princess Margaret Hospital , Toronto , Canada (PB); Department of Genetics, Institut Curie , Paris , France (GP, CC, ER, IB); Department of Pathology, Institut Curie , Paris , France (AVS); Institut Curie / INSERM U900 , Paris , France (NS, XP); Department of Surgery, Institut Curie , Paris & Saint-Cloud , France (RR); Institut Curie, INSERM U830 , Paris , France (OD); EA7331, University of Paris-Descartes , Paris , France (IB).
authors.forename: Christophe
authors.initials: C
authors.lastname: Le Tourneau
authors.affiliation: Affiliations of authors:Department of Medical Oncology, Institut Curie , Paris & Saint-Cloud , France (CLT, MK, MA); EA7285 Versailles-St-Quentin-en-Yvelines University , France (CLT, RR); Investigational Cancer Therapeutics, M. D. Anderson Cancer Center , Houston, TX (AMT); Drug Development Program, Department of Medical Oncology and Hematology, Princess Margaret Hospital , Toronto , Canada (PB); Department of Genetics, Institut Curie , Paris , France (GP, CC, ER, IB); Department of Pathology, Institut Curie , Paris , France (AVS); Institut Curie / INSERM U900 , Paris , France (NS, XP); Department of Surgery, Institut Curie , Paris & Saint-Cloud , France (RR); Institut Curie, INSERM U830 , Paris , France (OD); EA7331, University of Paris-Descartes , Paris , France (IB).
authors.forename: Maud
authors.initials: M
authors.lastname: Kamal
authors.affiliation: Affiliations of authors:Department of Medical Oncology, Institut Curie , Paris & Saint-Cloud , France (CLT, MK, MA); EA7285 Versailles-St-Quentin-en-Yvelines University , France (CLT, RR); Investigational Cancer Therapeutics, M. D. Anderson Cancer Center , Houston, TX (AMT); Drug Development Program, Department of Medical Oncology and Hematology, Princess Margaret Hospital , Toronto , Canada (PB); Department of Genetics, Institut Curie , Paris , France (GP, CC, ER, IB); Department of Pathology, Institut Curie , Paris , France (AVS); Institut Curie / INSERM U900 , Paris , France (NS, XP); Department of Surgery, Institut Curie , Paris & Saint-Cloud , France (RR); Institut Curie, INSERM U830 , Paris , France (OD); EA7331, University of Paris-Descartes , Paris , France (IB).
authors.forename: Apostolia-Maria
authors.initials: AM
authors.lastname: Tsimberidou
authors.affiliation: Affiliations of authors:Department of Medical Oncology, Institut Curie , Paris & Saint-Cloud , France (CLT, MK, MA); EA7285 Versailles-St-Quentin-en-Yvelines University , France (CLT, RR); Investigational Cancer Therapeutics, M. D. Anderson Cancer Center , Houston, TX (AMT); Drug Development Program, Department of Medical Oncology and Hematology, Princess Margaret Hospital , Toronto , Canada (PB); Department of Genetics, Institut Curie , Paris , France (GP, CC, ER, IB); Department of Pathology, Institut Curie , Paris , France (AVS); Institut Curie / INSERM U900 , Paris , France (NS, XP); Department of Surgery, Institut Curie , Paris & Saint-Cloud , France (RR); Institut Curie, INSERM U830 , Paris , France (OD); EA7331, University of Paris-Descartes , Paris , France (IB).
authors.forename: Philippe
authors.initials: P
authors.lastname: Bedard
authors.affiliation: Affiliations of authors:Department of Medical Oncology, Institut Curie , Paris & Saint-Cloud , France (CLT, MK, MA); EA7285 Versailles-St-Quentin-en-Yvelines University , France (CLT, RR); Investigational Cancer Therapeutics, M. D. Anderson Cancer Center , Houston, TX (AMT); Drug Development Program, Department of Medical Oncology and Hematology, Princess Margaret Hospital , Toronto , Canada (PB); Department of Genetics, Institut Curie , Paris , France (GP, CC, ER, IB); Department of Pathology, Institut Curie , Paris , France (AVS); Institut Curie / INSERM U900 , Paris , France (NS, XP); Department of Surgery, Institut Curie , Paris & Saint-Cloud , France (RR); Institut Curie, INSERM U830 , Paris , France (OD); EA7331, University of Paris-Descartes , Paris , France (IB).
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Pierron
authors.affiliation: Affiliations of authors:Department of Medical Oncology, Institut Curie , Paris & Saint-Cloud , France (CLT, MK, MA); EA7285 Versailles-St-Quentin-en-Yvelines University , France (CLT, RR); Investigational Cancer Therapeutics, M. D. Anderson Cancer Center , Houston, TX (AMT); Drug Development Program, Department of Medical Oncology and Hematology, Princess Margaret Hospital , Toronto , Canada (PB); Department of Genetics, Institut Curie , Paris , France (GP, CC, ER, IB); Department of Pathology, Institut Curie , Paris , France (AVS); Institut Curie / INSERM U900 , Paris , France (NS, XP); Department of Surgery, Institut Curie , Paris & Saint-Cloud , France (RR); Institut Curie, INSERM U830 , Paris , France (OD); EA7331, University of Paris-Descartes , Paris , France (IB).
authors.forename: Céline
authors.initials: C
authors.lastname: Callens
authors.affiliation: Affiliations of authors:Department of Medical Oncology, Institut Curie , Paris & Saint-Cloud , France (CLT, MK, MA); EA7285 Versailles-St-Quentin-en-Yvelines University , France (CLT, RR); Investigational Cancer Therapeutics, M. D. Anderson Cancer Center , Houston, TX (AMT); Drug Development Program, Department of Medical Oncology and Hematology, Princess Margaret Hospital , Toronto , Canada (PB); Department of Genetics, Institut Curie , Paris , France (GP, CC, ER, IB); Department of Pathology, Institut Curie , Paris , France (AVS); Institut Curie / INSERM U900 , Paris , France (NS, XP); Department of Surgery, Institut Curie , Paris & Saint-Cloud , France (RR); Institut Curie, INSERM U830 , Paris , France (OD); EA7331, University of Paris-Descartes , Paris , France (IB).
authors.forename: Etienne
authors.initials: E
authors.lastname: Rouleau
authors.affiliation: Affiliations of authors:Department of Medical Oncology, Institut Curie , Paris & Saint-Cloud , France (CLT, MK, MA); EA7285 Versailles-St-Quentin-en-Yvelines University , France (CLT, RR); Investigational Cancer Therapeutics, M. D. Anderson Cancer Center , Houston, TX (AMT); Drug Development Program, Department of Medical Oncology and Hematology, Princess Margaret Hospital , Toronto , Canada (PB); Department of Genetics, Institut Curie , Paris , France (GP, CC, ER, IB); Department of Pathology, Institut Curie , Paris , France (AVS); Institut Curie / INSERM U900 , Paris , France (NS, XP); Department of Surgery, Institut Curie , Paris & Saint-Cloud , France (RR); Institut Curie, INSERM U830 , Paris , France (OD); EA7331, University of Paris-Descartes , Paris , France (IB).
authors.forename: Anne
authors.initials: A
authors.lastname: Vincent-Salomon
authors.affiliation: Affiliations of authors:Department of Medical Oncology, Institut Curie , Paris & Saint-Cloud , France (CLT, MK, MA); EA7285 Versailles-St-Quentin-en-Yvelines University , France (CLT, RR); Investigational Cancer Therapeutics, M. D. Anderson Cancer Center , Houston, TX (AMT); Drug Development Program, Department of Medical Oncology and Hematology, Princess Margaret Hospital , Toronto , Canada (PB); Department of Genetics, Institut Curie , Paris , France (GP, CC, ER, IB); Department of Pathology, Institut Curie , Paris , France (AVS); Institut Curie / INSERM U900 , Paris , France (NS, XP); Department of Surgery, Institut Curie , Paris & Saint-Cloud , France (RR); Institut Curie, INSERM U830 , Paris , France (OD); EA7331, University of Paris-Descartes , Paris , France (IB).
authors.forename: Nicolas
authors.initials: N
authors.lastname: Servant
authors.affiliation: Affiliations of authors:Department of Medical Oncology, Institut Curie , Paris & Saint-Cloud , France (CLT, MK, MA); EA7285 Versailles-St-Quentin-en-Yvelines University , France (CLT, RR); Investigational Cancer Therapeutics, M. D. Anderson Cancer Center , Houston, TX (AMT); Drug Development Program, Department of Medical Oncology and Hematology, Princess Margaret Hospital , Toronto , Canada (PB); Department of Genetics, Institut Curie , Paris , France (GP, CC, ER, IB); Department of Pathology, Institut Curie , Paris , France (AVS); Institut Curie / INSERM U900 , Paris , France (NS, XP); Department of Surgery, Institut Curie , Paris & Saint-Cloud , France (RR); Institut Curie, INSERM U830 , Paris , France (OD); EA7331, University of Paris-Descartes , Paris , France (IB).
authors.forename: Marie
authors.initials: M
authors.lastname: Alt
authors.affiliation: Affiliations of authors:Department of Medical Oncology, Institut Curie , Paris & Saint-Cloud , France (CLT, MK, MA); EA7285 Versailles-St-Quentin-en-Yvelines University , France (CLT, RR); Investigational Cancer Therapeutics, M. D. Anderson Cancer Center , Houston, TX (AMT); Drug Development Program, Department of Medical Oncology and Hematology, Princess Margaret Hospital , Toronto , Canada (PB); Department of Genetics, Institut Curie , Paris , France (GP, CC, ER, IB); Department of Pathology, Institut Curie , Paris , France (AVS); Institut Curie / INSERM U900 , Paris , France (NS, XP); Department of Surgery, Institut Curie , Paris & Saint-Cloud , France (RR); Institut Curie, INSERM U830 , Paris , France (OD); EA7331, University of Paris-Descartes , Paris , France (IB).
authors.forename: Roman
authors.initials: R
authors.lastname: Rouzier
authors.affiliation: Affiliations of authors:Department of Medical Oncology, Institut Curie , Paris & Saint-Cloud , France (CLT, MK, MA); EA7285 Versailles-St-Quentin-en-Yvelines University , France (CLT, RR); Investigational Cancer Therapeutics, M. D. Anderson Cancer Center , Houston, TX (AMT); Drug Development Program, Department of Medical Oncology and Hematology, Princess Margaret Hospital , Toronto , Canada (PB); Department of Genetics, Institut Curie , Paris , France (GP, CC, ER, IB); Department of Pathology, Institut Curie , Paris , France (AVS); Institut Curie / INSERM U900 , Paris , France (NS, XP); Department of Surgery, Institut Curie , Paris & Saint-Cloud , France (RR); Institut Curie, INSERM U830 , Paris , France (OD); EA7331, University of Paris-Descartes , Paris , France (IB).
authors.forename: Xavier
authors.initials: X
authors.lastname: Paoletti
authors.affiliation: Affiliations of authors:Department of Medical Oncology, Institut Curie , Paris & Saint-Cloud , France (CLT, MK, MA); EA7285 Versailles-St-Quentin-en-Yvelines University , France (CLT, RR); Investigational Cancer Therapeutics, M. D. Anderson Cancer Center , Houston, TX (AMT); Drug Development Program, Department of Medical Oncology and Hematology, Princess Margaret Hospital , Toronto , Canada (PB); Department of Genetics, Institut Curie , Paris , France (GP, CC, ER, IB); Department of Pathology, Institut Curie , Paris , France (AVS); Institut Curie / INSERM U900 , Paris , France (NS, XP); Department of Surgery, Institut Curie , Paris & Saint-Cloud , France (RR); Institut Curie, INSERM U830 , Paris , France (OD); EA7331, University of Paris-Descartes , Paris , France (IB).
authors.forename: Olivier
authors.initials: O
authors.lastname: Delattre
authors.affiliation: Affiliations of authors:Department of Medical Oncology, Institut Curie , Paris & Saint-Cloud , France (CLT, MK, MA); EA7285 Versailles-St-Quentin-en-Yvelines University , France (CLT, RR); Investigational Cancer Therapeutics, M. D. Anderson Cancer Center , Houston, TX (AMT); Drug Development Program, Department of Medical Oncology and Hematology, Princess Margaret Hospital , Toronto , Canada (PB); Department of Genetics, Institut Curie , Paris , France (GP, CC, ER, IB); Department of Pathology, Institut Curie , Paris , France (AVS); Institut Curie / INSERM U900 , Paris , France (NS, XP); Department of Surgery, Institut Curie , Paris & Saint-Cloud , France (RR); Institut Curie, INSERM U830 , Paris , France (OD); EA7331, University of Paris-Descartes , Paris , France (IB).
authors.forename: Ivan
authors.initials: I
authors.lastname: Bièche
mesh_terms: D000465:Algorithms; D014408:Biomarkers, Tumor / Q000235:genetics; D002986:Clinical Trials as Topic; D056915:DNA Copy Number Variations; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing / Q000187:drug effects; D016147:Genes, Tumor Suppressor / Q000187:drug effects; D059014:High-Throughput Nucleotide Sequencing; D057166:High-Throughput Screening Assays; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends*; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy*; D057285:Precision Medicine / Q000379:methods* / Q000639:trends; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D014408:Biomarkers, Tumor