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A genome-wide in vivo CRISPR activation screen identifies BACE1 as a therapeutic vulnerability of lung cancer brain metastasis.

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Title: A genome-wide in vivo CRISPR activation screen identifies BACE1 as a therapeutic vulnerability of lung cancer brain metastasis.
Authors: Chafe SC; Department of Surgery, McMaster University, Hamilton, ON L8S 4L8, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4L8, Canada., Zhai K; Department of Surgery, McMaster University, Hamilton, ON L8S 4L8, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4L8, Canada.; Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA., Aghaei N; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4L8, Canada., Miletic P; Department of Surgery, McMaster University, Hamilton, ON L8S 4L8, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4L8, Canada., Huang Z; Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA., Brown KR; Hospital for Sick Children, Toronto, ON M5G 1E8, Canada., Mobilio D; Department of Surgery, McMaster University, Hamilton, ON L8S 4L8, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4L8, Canada., Young D; Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada.; Snyder Institute for Chronic Diseases, Hotchkiss Brain Institute and McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada., Suk Y; Department of Surgery, McMaster University, Hamilton, ON L8S 4L8, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4L8, Canada., Grewal S; Department of Surgery, McMaster University, Hamilton, ON L8S 4L8, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4L8, Canada., McKenna D; Department of Surgery, McMaster University, Hamilton, ON L8S 4L8, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4L8, Canada., Alizada Z; Department of Surgery, McMaster University, Hamilton, ON L8S 4L8, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4L8, Canada., Kieliszek AM; Department of Surgery, McMaster University, Hamilton, ON L8S 4L8, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4L8, Canada., Lam FC; Department of Neurosurgery, Stanford School of Medicine, Palo Alto, CA 94305, USA., Escudero L; Department of Surgery, McMaster University, Hamilton, ON L8S 4L8, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4L8, Canada., Huang Q; Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA., Huebner A; Cancer Evolution and Genome Instability Laboratory, Francis Crick Institute, London NW1 1AT, UK.; Department of Medical Oncology, Cancer Research UK Lung Cancer Centre of Excellence, UCL Cancer Institute, University College London, London WCE1 6DD, UK., Lu J; Department of Surgery, McMaster University, Hamilton, ON L8S 4L8, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4L8, Canada., Ang P; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4L8, Canada.; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4L8, Canada., Anand A; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4L8, Canada.; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4L8, Canada., Custers S; Department of Surgery, McMaster University, Hamilton, ON L8S 4L8, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4L8, Canada., Apel E; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4L8, Canada.; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4L8, Canada., Slassi S; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4L8, Canada.; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4L8, Canada., Brakel B; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4L8, Canada.; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4L8, Canada., Kim J; Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA., Liu JKC; Department of Neuro-oncology, Moffitt Cancer Center, Tampa, FL 33612, USA., Bassey-Archibong BI; Department of Biological Sciences, Concordia University of Edmonton, Edmonton, AB T5B 4E3, Canada., Abdo R; Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada.; Department of Pathology and Molecular Medicine, Western University, London, ON N6A 5C1, Canada., Shargall Y; Department of Surgery, McMaster University, Hamilton, ON L8S 4L8, Canada.; Division of Thoracic Surgery, McMaster University, Hamilton, ON L8S 4K1, Canada., Lu JQ; Department of Pathology and Laboratory Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada., Cutz JC; Department of Pathology and Laboratory Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada., Zhang Q; Department of Pathology and Molecular Medicine, Western University, London, ON N6A 5C1, Canada.; Department of Pathology and Laboratory Medicine, London Health Sciences Centre, London, ON N6A 5A5, Canada., Li SS; Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada., Venugopal C; Department of Surgery, McMaster University, Hamilton, ON L8S 4L8, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4L8, Canada., Hynds RE; Epithelial Cell Biology in ENT Research Group, Developmental Biology and Cancer Department, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK., Dufour A; Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada.; Snyder Institute for Chronic Diseases, Hotchkiss Brain Institute and McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada., Moffat J; Hospital for Sick Children, Toronto, ON M5G 1E8, Canada., Swanton C; Cancer Evolution and Genome Instability Laboratory, Francis Crick Institute, London NW1 1AT, UK.; Department of Medical Oncology, Cancer Research UK Lung Cancer Centre of Excellence, UCL Cancer Institute, University College London, London WCE1 6DD, UK., Bao S; Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.; Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.; Center for Cancer Stem Cell Research, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA., Singh SK; Department of Surgery, McMaster University, Hamilton, ON L8S 4L8, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4L8, Canada.; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4L8, Canada.
Source: Science translational medicine [Sci Transl Med] 2025 Jul 02; Vol. 17 (805), pp. eadu2459. Date of Electronic Publication: 2025 Jul 02.
Publication Type: Journal Article
Journal Info: Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101505086 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1946-6242 (Electronic) Linking ISSN: 19466234 NLM ISO Abbreviation: Sci Transl Med Subsets: MEDLINE
Database: MEDLINE Ultimate
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  Data: A genome-wide in vivo CRISPR activation screen identifies BACE1 as a therapeutic vulnerability of lung cancer brain metastasis.
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  Data: <searchLink fieldCode="AU" term="%22Chafe+SC%22">Chafe SC</searchLink>; Department of Surgery, McMaster University, Hamilton, ON L8S 4L8, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4L8, Canada.<br /><searchLink fieldCode="AU" term="%22Zhai+K%22">Zhai K</searchLink>; Department of Surgery, McMaster University, Hamilton, ON L8S 4L8, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4L8, Canada.; Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.<br /><searchLink fieldCode="AU" term="%22Aghaei+N%22">Aghaei N</searchLink>; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4L8, Canada.<br /><searchLink fieldCode="AU" term="%22Miletic+P%22">Miletic P</searchLink>; Department of Surgery, McMaster University, Hamilton, ON L8S 4L8, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4L8, Canada.<br /><searchLink fieldCode="AU" term="%22Huang+Z%22">Huang Z</searchLink>; 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Department of Neurosurgery, Stanford School of Medicine, Palo Alto, CA 94305, USA.<br /><searchLink fieldCode="AU" term="%22Escudero+L%22">Escudero L</searchLink>; Department of Surgery, McMaster University, Hamilton, ON L8S 4L8, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4L8, Canada.<br /><searchLink fieldCode="AU" term="%22Huang+Q%22">Huang Q</searchLink>; Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.<br /><searchLink fieldCode="AU" term="%22Huebner+A%22">Huebner A</searchLink>; Cancer Evolution and Genome Instability Laboratory, Francis Crick Institute, London NW1 1AT, UK.; Department of Medical Oncology, Cancer Research UK Lung Cancer Centre of Excellence, UCL Cancer Institute, University College London, London WCE1 6DD, UK.<br /><searchLink fieldCode="AU" term="%22Lu+J%22">Lu J</searchLink>; Department of Surgery, McMaster University, Hamilton, ON L8S 4L8, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4L8, Canada.<br /><searchLink fieldCode="AU" term="%22Ang+P%22">Ang P</searchLink>; 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Hospital for Sick Children, Toronto, ON M5G 1E8, Canada.<br /><searchLink fieldCode="AU" term="%22Swanton+C%22">Swanton C</searchLink>; Cancer Evolution and Genome Instability Laboratory, Francis Crick Institute, London NW1 1AT, UK.; Department of Medical Oncology, Cancer Research UK Lung Cancer Centre of Excellence, UCL Cancer Institute, University College London, London WCE1 6DD, UK.<br /><searchLink fieldCode="AU" term="%22Bao+S%22">Bao S</searchLink>; Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.; Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.; Center for Cancer Stem Cell Research, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.<br /><searchLink fieldCode="AU" term="%22Singh+SK%22">Singh SK</searchLink>; Department of Surgery, McMaster University, Hamilton, ON L8S 4L8, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4L8, Canada.; 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