Individualized Systems Medicine Strategy to Tailor Treatments for Patients with Chemorefractory Acute Myeloid Leukemia
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- Tea Pemovska
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Mika Kontro
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Bhagwan Yadav
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Henrik Edgren
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Samuli Eldfors
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Agnieszka Szwajda
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Henrikki Almusa
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Maxim M. Bespalov
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Pekka Ellonen
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Erkki Elonen
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Bjørn T. Gjertsen
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Riikka Karjalainen
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Evgeny Kulesskiy
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Sonja Lagström
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Anna Lehto
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Maija Lepistö
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Tuija Lundán
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Muntasir Mamun Majumder
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Jesus M. Lopez Marti
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Pirkko Mattila
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Astrid Murumägi
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Satu Mustjoki
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Aino Palva
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Alun Parsons
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Tero Pirttinen
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Maria E. Rämet
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Minna Suvela
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Laura Turunen
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Imre Västrik
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Maija Wolf
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Jonathan Knowles
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Tero Aittokallio
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Caroline A. Heckman
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Kimmo Porkka
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Olli Kallioniemi
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
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- Krister Wennerberg
- Authors' Affiliations: 1Institute for Molecular Medicine Finland, FIMM; 2Hematology Research Unit Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki; 3Department of Clinical Chemistry and TYKSLAB, Turku University Central Hospital, University of Turku, Turku; 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 5Department of Clinical Science, Hematology Section, University of Bergen; and 6Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
Description
<jats:title>Abstract</jats:title> <jats:p>We present an individualized systems medicine (ISM) approach to optimize cancer drug therapies one patient at a time. ISM is based on (i) molecular profiling and ex vivo drug sensitivity and resistance testing (DSRT) of patients' cancer cells to 187 oncology drugs, (ii) clinical implementation of therapies predicted to be effective, and (iii) studying consecutive samples from the treated patients to understand the basis of resistance. Here, application of ISM to 28 samples from patients with acute myeloid leukemia (AML) uncovered five major taxonomic drug-response subtypes based on DSRT profiles, some with distinct genomic features (e.g., MLL gene fusions in subgroup IV and FLT3-ITD mutations in subgroup V). Therapy based on DSRT resulted in several clinical responses. After progression under DSRT-guided therapies, AML cells displayed significant clonal evolution and novel genomic changes potentially explaining resistance, whereas ex vivo DSRT data showed resistance to the clinically applied drugs and new vulnerabilities to previously ineffective drugs.</jats:p> <jats:p>Significance: Here, we demonstrate an ISM strategy to optimize safe and effective personalized cancer therapies for individual patients as well as to understand and predict disease evolution and the next line of therapy. This approach could facilitate systematic drug repositioning of approved targeted drugs as well as help to prioritize and de-risk emerging drugs for clinical testing. Cancer Discov; 3(12); 1416–29. ©2013 AACR.</jats:p> <jats:p>See related commentary by Hourigan and Karp, p. 1336</jats:p> <jats:p>This article is highlighted in the In This Issue feature, p. 1317</jats:p>
Journal
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- Cancer Discovery
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Cancer Discovery 3 (12), 1416-1429, 2013-12-01
American Association for Cancer Research (AACR)
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Details 詳細情報について
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- CRID
- 1362825894378358400
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- ISSN
- 21598290
- 21598274
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- Data Source
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- Crossref