Implementing a Functional Precision Medicine Tumor Board for Acute Myeloid Leukemia.

Autor:	Malani D; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland., Kumar A; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland., Brück O; Hematology Research Unit Helsinki, University of Helsinki, and Helsinki University Hospital Comprehensive Cancer Center, Department of Hematology, Helsinki, Finland.; Translational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki, Helsinki, Finland.; iCAN Digital Precision Cancer Medicine Flagship, Helsinki, Finland., Kontro M; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.; Hematology Research Unit Helsinki, University of Helsinki, and Helsinki University Hospital Comprehensive Cancer Center, Department of Hematology, Helsinki, Finland., Yadav B; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.; Hematology Research Unit Helsinki, University of Helsinki, and Helsinki University Hospital Comprehensive Cancer Center, Department of Hematology, Helsinki, Finland., Hellesøy M; Department of Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway.; Center for Cancer Biomarkers (CCBIO), Department of Clinical Science, University of Bergen, Bergen, Norway., Kuusanmäki H; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.; Biotech Research & Innovation Centre (BRIC) and Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), University of Copenhagen, Copenhagen, Denmark., Dufva O; Hematology Research Unit Helsinki, University of Helsinki, and Helsinki University Hospital Comprehensive Cancer Center, Department of Hematology, Helsinki, Finland.; Translational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki, Helsinki, Finland., Kankainen M; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.; Hematology Research Unit Helsinki, University of Helsinki, and Helsinki University Hospital Comprehensive Cancer Center, Department of Hematology, Helsinki, Finland.; Translational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki, Helsinki, Finland.; iCAN Digital Precision Cancer Medicine Flagship, Helsinki, Finland., Eldfors S; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.; Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts, USA., Potdar S; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland., Saarela J; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland., Turunen L; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland., Parsons A; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland., Västrik I; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland., Kivinen K; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland., Saarela J; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.; Centre for Molecular Medicine Norway, NCMM, University of Oslo, Oslo, Norway., Räty R; Hematology Research Unit Helsinki, University of Helsinki, and Helsinki University Hospital Comprehensive Cancer Center, Department of Hematology, Helsinki, Finland., Lehto M; Hematology Research Unit Helsinki, University of Helsinki, and Helsinki University Hospital Comprehensive Cancer Center, Department of Hematology, Helsinki, Finland., Wolf M; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland., Gjertsen BT; Department of Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway.; Center for Cancer Biomarkers (CCBIO), Department of Clinical Science, University of Bergen, Bergen, Norway., Mustjoki S; Hematology Research Unit Helsinki, University of Helsinki, and Helsinki University Hospital Comprehensive Cancer Center, Department of Hematology, Helsinki, Finland.; Translational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki, Helsinki, Finland.; iCAN Digital Precision Cancer Medicine Flagship, Helsinki, Finland., Aittokallio T; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.; Institute for Cancer Research, Oslo University Hospital, and Oslo Centre for Biostatistics and Epidemiology, University of Oslo, Norway., Wennerberg K; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.; Biotech Research & Innovation Centre (BRIC) and Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), University of Copenhagen, Copenhagen, Denmark., Heckman CA; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.; iCAN Digital Precision Cancer Medicine Flagship, Helsinki, Finland., Kallioniemi O; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland. kimmo.porkka@helsinki.fi olli.kallioniemi@scilifelab.se.; iCAN Digital Precision Cancer Medicine Flagship, Helsinki, Finland.; Science for Life Laboratory, Department of Oncology and Pathology, Karolinska Institutet, Solna, Sweden., Porkka K; Hematology Research Unit Helsinki, University of Helsinki, and Helsinki University Hospital Comprehensive Cancer Center, Department of Hematology, Helsinki, Finland. kimmo.porkka@helsinki.fi olli.kallioniemi@scilifelab.se.; iCAN Digital Precision Cancer Medicine Flagship, Helsinki, Finland.
Jazyk:	angličtina
Zdroj:	Cancer discovery [Cancer Discov] 2022 Feb; Vol. 12 (2), pp. 388-401. Date of Electronic Publication: 2021 Nov 17.
DOI:	10.1158/2159-8290.CD-21-0410
Abstrakt:	We generated ex vivo drug-response and multiomics profiling data for a prospective series of 252 samples from 186 patients with acute myeloid leukemia (AML). A functional precision medicine tumor board (FPMTB) integrated clinical, molecular, and functional data for application in clinical treatment decisions. Actionable drugs were found for 97% of patients with AML, and the recommendations were clinically implemented in 37 relapsed or refractory patients. We report a 59% objective response rate for the individually tailored therapies, including 13 complete responses, as well as bridging five patients with AML to allogeneic hematopoietic stem cell transplantation. Data integration across all cases enabled the identification of drug response biomarkers, such as the association of IL15 overexpression with resistance to FLT3 inhibitors. Integration of molecular profiling and large-scale drug response data across many patients will enable continuous improvement of the FPMTB recommendations, providing a paradigm for individualized implementation of functional precision cancer medicine. SIGNIFICANCE: Oncogenomics data can guide clinical treatment decisions, but often such data are neither actionable nor predictive. Functional ex vivo drug testing contributes significant additional, clinically actionable therapeutic insights for individual patients with AML. Such data can be generated in four days, enabling rapid translation through FPMTB. See related commentary by Letai, p. 290 . This article is highlighted in the In This Issue feature, p. 275 . (©2021 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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