Targeting the interaction of paracrine-mediated LIF for the treatment and monitoring of pancreatic cancer

by



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  1. Current Address: Trovagene, San Diego, CA, USA

  2. Current address: Crown Bioscience San Diego, San Diego, California, USA

  3. These authors also contributed: Weina Gao, Nikki K. Lytle

  4. Deceased: Tony Pawson

Affiliations

  1. Laboratory of Molecular and Cell Biology, Salk Institute of Biological Studies, La Jolla, California, USA

    • Yu Shi
    • , Huaiyu Sun
    • , Jill Meisenhelder
    • Elena Terenziani
    • , Gyunghwi Woo
    • And Tony Hunter

  2. Department of Chemistry, Southern Science and Technology University, Shenzhen, China

    • Weina Gao
    • , Peiwu Huang
    • , Xiao Yuan
    • & Ruijun Tian

  3. Key Laboratory of Micro-Cell Environment of South Shenzhen University, China

    • Weina Gao
    • , Peiwu Huang
    • , Xiao Yuan
    • & Ruijun Tian

  4. Department of Pharmacology, Faculty of Medicine at the University of California at San Diego, La Jolla, California, USA

    • Nikki K. Lytle
    • And Tannishtha Reya

  5. Sanford Consortium for Regenerative Medicine, La Jolla, California, USA

    • Nikki K. Lytle
    • And Tannishtha Reya

  6. Key State Laboratory of Biological and Environmental Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China

  7. Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA

    • Amanda M. Dann
    • And Timothy R. Donahue

  8. Gene Expression Laboratory, Salk Institute of Biological Studies, La Jolla, California, USA

    • Maya Ridinger-Season
    • Kathleen E. DelGiorno
    • , Corina E. Antal
    • Gaoyang Liang
    • Annette R. Atkins
    • Mathias Leblanc
    • Michael Downes
    • Ronald M. Evans
    • And Geoffrey M. Wahl

  9. Integrative genomics and bioinformatics, Salk Institute of Biological Studies, La Jolla, California, USA

  10. Waitt Advanced Biophotonics Center, Salk Biological Studies Institute, La Jolla, California, USA

    • Linjing Fang
    • , Thom P. Santisakultarm
    • & Uri Manor

  11. Institute of Oncology, Shenzhen People's Hospital, Shenzhen, China

  12. Texas Oncology – Baylor University Medical Center, Dallas, Texas, USA

  13. Translational Genomics Research Institute, Scottsdale, Arizona, USA

    • Erkut Borazanci
    • & Daniel D. Von Hoff

  14. HonorHealth, Scottsdale, AZ, USA

    • Erkut Borazanci
    • & Daniel D. Von Hoff

  15. Eppley Institute for Cancer Research and Related Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA

    • Paul M. Grandgenett
    • And Michael A. Hollingsworth

  16. Department of Pathology, University of California at San Francisco, San Francisco, California, USA

  17. Hematology Oncology, Department of Medicine, University of California at San Francisco, San Francisco, California, USA

  18. Functional MRI Center, Department of Radiology, University of California at San Diego, La Jolla, California, USA.

  19. Department of Surgery, Division of Surgical Oncology, Faculty of Medicine, University of California, San Diego, La Jolla, California, USA

  20. Moores Cancer Center, School of Medicine at the University of California at San Diego, La Jolla, California, USA

  21. Howard Hughes Medical Institute, Salk Institute of Biological Studies, La Jolla, California, USA

  22. Lunenfeld – Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada

    • Tony Pawson
    • & Ruijun Tian

  23. Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada

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contributions

Y.S. designed the project, planned the research, carried out or participated in all the experiments and drafted the document. W.G. performed mass spectrometry tests and helped prepare the figures. N.K.L. and T.R. performed and analyzed data relating to the tumor-initiating cells. P.H. and X.Y. performed PRM-MS. A.M.D. and T.R.D. provided human pancreatic tissue and FFPE specimens, and performed correlation analysis. MRS. and K.E.D. provided reagents and participated in some mouse studies. C.E.A., G.L. and A.R.A. provided CSPs and organoids. G.E. and H.S. analyzes RNA-seq data. J.M., E.T. and G.W. provide laboratory and animal support L.F., T.P.S. and U.M. developed algorithms for image quantization. R.X. provided samples of cancerous tissue and a consultation in pathology. D.D.V.H., C.R.B., E.B., P.M.G. and M.A.H. provided samples of human PDAC serum. M.L., S.E.U. and E.A.C. Pathological classification carried out. MRS. provided advice for fMRI. A.M.L. provided human serum samples, pathological evaluation and handwritten comments. M.D., R.M.E., and G.M.W. provided intellectual support and handwritten comments. T.P. participated in the initial design of the project. R.T. designed mass spectrometry screening, designed and participated in all mass spectrometry tests and drafted the document. T.H. designed and supervised the project and wrote the paper.

Competing interests

E.B. is scientific advisor to Fujifilm, Ipsen and Corcept. D.D.V.H. is an employee of McKesson, co-founder of Stromatis Pharma and Systems Oncology, and shareholder of McKesson, Medtronic, CerRx, SynDevRx, UnitedHealthare, Anthem, Capella Therapeutics and Cell Therapeutics. D.D.V.H. is a scientific advisor to DNAtrix, Esperance, Five Prime, Imaging Criteria, Immoduon, Insys, Institute for Medical Prognosis, Themeutic Therapeutics, Senhwa Biosciences, Tolero, Trovagene, Alpha Cancer Technologies, Arvinas, Bellicum, CanBas, CanBas, Horizon Discovery, Innocent Oncolyze, RenovoRx, TD2, AADI, Bioscience Biology, BiolineRx, CV6, CytomX, EMD Serono, Evelo, Fujifilm, Histogen, Intezyne, Kalos, Kura, Phosplatin, SOTIO, Strategia, Sun Biopharma, Actinium Synergene, Aduro Biotech , ARMO BioSciences, Anti-Cancer Pharmaceuticals, Defined Health, Geistlich Pharma, HUYA Bioscience, Immunophotonics, Novocure, ARIAD, Boston Biomedical, Corrona, Forma, Genzada, LEAF, Oncology Ventilation, Reflexion, Medical Medicine, Fate, FibroGen, Jounce Therapy, Therapeutics Samus, Sumitomo Dainippon, Aeglea Biotherapeutics, Oncology 2X, Innokeys, Novita, NuCana BioMed, Araxes, Ipsen, SciClone, TargaGenix, Trans Med, Veana Ther Apeutics, B Technologies Ipecific, Riptide Bioscience, Vicus Therapeutics, Codiak Biosciences, Decoy Biosystems, OSSI, Agenus, Life Science Globe, Kelun – Klus Pharma, Radimmune, Samumed, SOBI, Bio Adicet, BioXCel Therapeutics, Bryology, Helgorie,, AiMed Bio, Boston Scientific, Corcept, Erimos and Gimbal.

Corresponding authors

Correspondence to
Yu Shi or Ruijun Tian or Tony Hunter.

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