title: National Cancer Institute's Precision Medicine Initiatives for the new National Clinical Trials Network.
abstract: The promise of precision medicine will only be fully realized if the research community can adapt its clinical trials methodology to study molecularly characterized tumors instead of the traditional histologic classification. Such trials will depend on adequate tissue collection, availability of quality controlled, high throughput molecular assays, and the ability to screen large numbers of tumors to find those with the desired molecular alterations. The National Cancer Institute's (NCI) new National Clinical Trials Network (NCTN) is well positioned to conduct such trials. The NCTN has the ability to seamlessly perform ethics review, register patients, manage data, and deliver investigational drugs across its many sites including both in cities and rural communities, academic centers, and private practices. The initial set of trials will focus on different questions: (1) Exceptional Responders Initiative-why do a minority of patients with solid tumors or lymphoma respond very well to some drugs even if the majority do not?; (2) NCI MATCH trial-can molecular markers predict response to targeted therapies in patients with advanced cancer resistant to standard treatment?; (3) ALCHEMIST trial-will targeted epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors improve survival for adenocarcinoma of the lung in the adjuvant setting?; and (4) Lung Cancer Master Protocol trial for advanced squamous cell lung cancer-is there an advantage to developing drugs for small subsets of molecularly characterized tumors in a single, multiarm trial design? These studies will hopefully spawn a new era of treatment trials that will carefully select the tumors that may respond best to investigational therapy.
authors.affiliation: From the Division of Cancer Treatment and Diagnosis, National Cancer Institute at the National Institutes of Health, Bethesda, MD; Center for Cancer Genomics, National Cancer Institute at the National Institutes of Health, Bethesda, MD; and Leidos Corporation, Frederick, MD.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Abrams
authors.affiliation: From the Division of Cancer Treatment and Diagnosis, National Cancer Institute at the National Institutes of Health, Bethesda, MD; Center for Cancer Genomics, National Cancer Institute at the National Institutes of Health, Bethesda, MD; and Leidos Corporation, Frederick, MD.
authors.forename: Barbara
authors.initials: B
authors.lastname: Conley
authors.affiliation: From the Division of Cancer Treatment and Diagnosis, National Cancer Institute at the National Institutes of Health, Bethesda, MD; Center for Cancer Genomics, National Cancer Institute at the National Institutes of Health, Bethesda, MD; and Leidos Corporation, Frederick, MD.
authors.forename: Margaret
authors.initials: M
authors.lastname: Mooney
authors.affiliation: From the Division of Cancer Treatment and Diagnosis, National Cancer Institute at the National Institutes of Health, Bethesda, MD; Center for Cancer Genomics, National Cancer Institute at the National Institutes of Health, Bethesda, MD; and Leidos Corporation, Frederick, MD.
authors.forename: James
authors.initials: J
authors.lastname: Zwiebel
authors.affiliation: From the Division of Cancer Treatment and Diagnosis, National Cancer Institute at the National Institutes of Health, Bethesda, MD; Center for Cancer Genomics, National Cancer Institute at the National Institutes of Health, Bethesda, MD; and Leidos Corporation, Frederick, MD.
authors.forename: Alice
authors.initials: A
authors.lastname: Chen
authors.affiliation: From the Division of Cancer Treatment and Diagnosis, National Cancer Institute at the National Institutes of Health, Bethesda, MD; Center for Cancer Genomics, National Cancer Institute at the National Institutes of Health, Bethesda, MD; and Leidos Corporation, Frederick, MD.
authors.forename: John J
authors.initials: JJ
authors.lastname: Welch
authors.affiliation: From the Division of Cancer Treatment and Diagnosis, National Cancer Institute at the National Institutes of Health, Bethesda, MD; Center for Cancer Genomics, National Cancer Institute at the National Institutes of Health, Bethesda, MD; and Leidos Corporation, Frederick, MD.
authors.forename: Naoko
authors.initials: N
authors.lastname: Takebe
authors.affiliation: From the Division of Cancer Treatment and Diagnosis, National Cancer Institute at the National Institutes of Health, Bethesda, MD; Center for Cancer Genomics, National Cancer Institute at the National Institutes of Health, Bethesda, MD; and Leidos Corporation, Frederick, MD.
authors.forename: Shakun
authors.initials: S
authors.lastname: Malik
authors.affiliation: From the Division of Cancer Treatment and Diagnosis, National Cancer Institute at the National Institutes of Health, Bethesda, MD; Center for Cancer Genomics, National Cancer Institute at the National Institutes of Health, Bethesda, MD; and Leidos Corporation, Frederick, MD.
authors.forename: Lisa
authors.initials: L
authors.lastname: McShane
authors.affiliation: From the Division of Cancer Treatment and Diagnosis, National Cancer Institute at the National Institutes of Health, Bethesda, MD; Center for Cancer Genomics, National Cancer Institute at the National Institutes of Health, Bethesda, MD; and Leidos Corporation, Frederick, MD.
authors.forename: Edward
authors.initials: E
authors.lastname: Korn
authors.affiliation: From the Division of Cancer Treatment and Diagnosis, National Cancer Institute at the National Institutes of Health, Bethesda, MD; Center for Cancer Genomics, National Cancer Institute at the National Institutes of Health, Bethesda, MD; and Leidos Corporation, Frederick, MD.
authors.forename: Mickey
authors.initials: M
authors.lastname: Williams
authors.affiliation: From the Division of Cancer Treatment and Diagnosis, National Cancer Institute at the National Institutes of Health, Bethesda, MD; Center for Cancer Genomics, National Cancer Institute at the National Institutes of Health, Bethesda, MD; and Leidos Corporation, Frederick, MD.
authors.forename: Louis
authors.initials: L
authors.lastname: Staudt
authors.affiliation: From the Division of Cancer Treatment and Diagnosis, National Cancer Institute at the National Institutes of Health, Bethesda, MD; Center for Cancer Genomics, National Cancer Institute at the National Institutes of Health, Bethesda, MD; and Leidos Corporation, Frederick, MD.
authors.forename: James
authors.initials: J
authors.lastname: Doroshow
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002986:Clinical Trials as Topic / Q000379:methods*; D004059:Diffusion of Innovation; D019008:Drug Resistance, Neoplasm; D020022:Genetic Predisposition to Disease; D006801:Humans; D008495:Medical Oncology / Q000379:methods*; D025202:Molecular Diagnostic Techniques; D058990:Molecular Targeted Therapy; D054547:National Cancer Institute (U.S.); D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018579:Patient Selection; D010641:Phenotype; D057285:Precision Medicine / Q000379:methods*; D011237:Predictive Value of Tests; D012042:Registries; D012107:Research Design; D016896:Treatment Outcome; D014481:United States
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor