Culture media composition influences patient-derived organoid ability to predict therapeutic responses in gastrointestinal cancers

Clinical MedicineOncologyTherapeutics Open Access | 10.1172/jci.insight.158060

Tara L. Hogenson,1 Hao Xie,2,3 William J. Phillips,1 Merih D. Toruner,1 Jenny J. Li,3 Isaac P. Horn,1 Devin J. Kennedy,1 Luciana L. Almada,1 David L. Marks,1 Ryan M. Carr,1 Murat Toruner,1 Ashley N. Sigafoos,1 Amanda N. Koenig-Kappes,1 Rachel L.O. Olson,1 Ezequiel J. Tolosa,1 Cheng Zhang,4 Hu Li,4 Jason D. Doles,5 Jonathan Bleeker,6 Michael T. Barrett,7 James H. Boyum,8 Benjamin R. Kipp,9 Amit Mahipal,3 Joleen M. Hubbard,3 Temperance J. Scheffler Hanson,3 Gloria M. Petersen,10 Surendra Dasari,11 Ann L. Oberg,11 Mark J. Truty,12 Rondell P. Graham,13 Michael J. Levy,14 Mojun Zhu,3 Daniel D. Billadeau,1 Alex A. Adjei,3 Nelson Dusetti,15 Juan L. Iovanna,15 Tanios S. Bekaii-Saab,7 Wen Wee Ma,3 and Martin E. Fernandez-Zapico1

1Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, Minnesota, USA.

2Department of Gastrointestinal Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

3Division of Medical Oncology, Department of Oncology,

4Department of Pharmacology, and

5Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.

6Sanford Research, Oncology, Sanford Health, Sioux Falls, South Dakota, USA.

7Division of Hematology/Oncology, Mayo Clinic, Phoenix, Arizona, USA.

8Department of Radiology,

9Department of Laboratory Medicine and Pathology,

10Division of Epidemiology, Department of Quantitative Health Sciences,

11Division of Computational Biology, Department of Quantitative Health Sciences, and

12Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.

13Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA.

14Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

15Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France.

Address correspondence to: Martin E. Fernandez-Zapico, Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.255.0285; Email: fernandezzapico.martin@mayo.edu. Or to: Wen Wee Ma, Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.293.0487; Email: ma.wen@mayo.edu.

Find articles by Hogenson, T. in: JCI | PubMed | Google Scholar

1Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, Minnesota, USA.

2Department of Gastrointestinal Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

3Division of Medical Oncology, Department of Oncology,

4Department of Pharmacology, and

5Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.

6Sanford Research, Oncology, Sanford Health, Sioux Falls, South Dakota, USA.

7Division of Hematology/Oncology, Mayo Clinic, Phoenix, Arizona, USA.

8Department of Radiology,

9Department of Laboratory Medicine and Pathology,

10Division of Epidemiology, Department of Quantitative Health Sciences,

11Division of Computational Biology, Department of Quantitative Health Sciences, and

12Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.

13Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA.

14Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

15Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France.

Address correspondence to: Martin E. Fernandez-Zapico, Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.255.0285; Email: fernandezzapico.martin@mayo.edu. Or to: Wen Wee Ma, Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.293.0487; Email: ma.wen@mayo.edu.

Find articles by Xie, H. in: JCI | PubMed | Google Scholar

1Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, Minnesota, USA.

2Department of Gastrointestinal Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

3Division of Medical Oncology, Department of Oncology,

4Department of Pharmacology, and

5Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.

6Sanford Research, Oncology, Sanford Health, Sioux Falls, South Dakota, USA.

7Division of Hematology/Oncology, Mayo Clinic, Phoenix, Arizona, USA.

8Department of Radiology,

9Department of Laboratory Medicine and Pathology,

10Division of Epidemiology, Department of Quantitative Health Sciences,

11Division of Computational Biology, Department of Quantitative Health Sciences, and

12Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.

13Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA.

14Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

15Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France.

Address correspondence to: Martin E. Fernandez-Zapico, Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.255.0285; Email: fernandezzapico.martin@mayo.edu. Or to: Wen Wee Ma, Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.293.0487; Email: ma.wen@mayo.edu.

Find articles by Phillips, W. in: JCI | PubMed | Google Scholar |

1Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, Minnesota, USA.

2Department of Gastrointestinal Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

3Division of Medical Oncology, Department of Oncology,

4Department of Pharmacology, and

5Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.

6Sanford Research, Oncology, Sanford Health, Sioux Falls, South Dakota, USA.

7Division of Hematology/Oncology, Mayo Clinic, Phoenix, Arizona, USA.

8Department of Radiology,

9Department of Laboratory Medicine and Pathology,

10Division of Epidemiology, Department of Quantitative Health Sciences,

11Division of Computational Biology, Department of Quantitative Health Sciences, and

12Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.

13Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA.

14Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

15Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France.

Address correspondence to: Martin E. Fernandez-Zapico, Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.255.0285; Email: fernandezzapico.martin@mayo.edu. Or to: Wen Wee Ma, Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.293.0487; Email: ma.wen@mayo.edu.

Find articles by Toruner, M. in: JCI | PubMed | Google Scholar

1Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, Minnesota, USA.

2Department of Gastrointestinal Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

3Division of Medical Oncology, Department of Oncology,

4Department of Pharmacology, and

5Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.

6Sanford Research, Oncology, Sanford Health, Sioux Falls, South Dakota, USA.

7Division of Hematology/Oncology, Mayo Clinic, Phoenix, Arizona, USA.

8Department of Radiology,

9Department of Laboratory Medicine and Pathology,

10Division of Epidemiology, Department of Quantitative Health Sciences,

11Division of Computational Biology, Department of Quantitative Health Sciences, and

12Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.

13Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA.

14Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

15Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France.

Address correspondence to: Martin E. Fernandez-Zapico, Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.255.0285; Email: fernandezzapico.martin@mayo.edu. Or to: Wen Wee Ma, Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.293.0487; Email: ma.wen@mayo.edu.

Find articles by Li, J. in: JCI | PubMed | Google Scholar |

1Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, Minnesota, USA.

2Department of Gastrointestinal Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

3Division of Medical Oncology, Department of Oncology,

4Department of Pharmacology, and

5Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.

6Sanford Research, Oncology, Sanford Health, Sioux Falls, South Dakota, USA.

7Division of Hematology/Oncology, Mayo Clinic, Phoenix, Arizona, USA.

8Department of Radiology,

9Department of Laboratory Medicine and Pathology,

10Division of Epidemiology, Department of Quantitative Health Sciences,

11Division of Computational Biology, Department of Quantitative Health Sciences, and

12Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.

13Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA.

14Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

15Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France.

Address correspondence to: Martin E. Fernandez-Zapico, Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.255.0285; Email: fernandezzapico.martin@mayo.edu. Or to: Wen Wee Ma, Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.293.0487; Email: ma.wen@mayo.edu.

Find articles by Horn, I. in: JCI | PubMed | Google Scholar

1Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, Minnesota, USA.

2Department of Gastrointestinal Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

3Division of Medical Oncology, Department of Oncology,

4Department of Pharmacology, and

5Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.

6Sanford Research, Oncology, Sanford Health, Sioux Falls, South Dakota, USA.

7Division of Hematology/Oncology, Mayo Clinic, Phoenix, Arizona, USA.

8Department of Radiology,

9Department of Laboratory Medicine and Pathology,

10Division of Epidemiology, Department of Quantitative Health Sciences,

11Division of Computational Biology, Department of Quantitative Health Sciences, and

12Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.

13Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA.

14Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

15Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France.

Address correspondence to: Martin E. Fernandez-Zapico, Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.255.0285; Email: fernandezzapico.martin@mayo.edu. Or to: Wen Wee Ma, Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.293.0487; Email: ma.wen@mayo.edu.

Find articles by Kennedy, D. in: JCI | PubMed | Google Scholar

1Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, Minnesota, USA.

2Department of Gastrointestinal Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

3Division of Medical Oncology, Department of Oncology,

4Department of Pharmacology, and

5Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.

6Sanford Research, Oncology, Sanford Health, Sioux Falls, South Dakota, USA.

7Division of Hematology/Oncology, Mayo Clinic, Phoenix, Arizona, USA.

8Department of Radiology,

9Department of Laboratory Medicine and Pathology,

10Division of Epidemiology, Department of Quantitative Health Sciences,

11Division of Computational Biology, Department of Quantitative Health Sciences, and

12Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.

13Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA.

14Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

15Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France.

Address correspondence to: Martin E. Fernandez-Zapico, Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.255.0285; Email: fernandezzapico.martin@mayo.edu. Or to: Wen Wee Ma, Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.293.0487; Email: ma.wen@mayo.edu.

Find articles by Almada, L. in: JCI | PubMed | Google Scholar

1Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, Minnesota, USA.

2Department of Gastrointestinal Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

3Division of Medical Oncology, Department of Oncology,

4Department of Pharmacology, and

5Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.

6Sanford Research, Oncology, Sanford Health, Sioux Falls, South Dakota, USA.

7Division of Hematology/Oncology, Mayo Clinic, Phoenix, Arizona, USA.

8Department of Radiology,

9Department of Laboratory Medicine and Pathology,

10Division of Epidemiology, Department of Quantitative Health Sciences,

11Division of Computational Biology, Department of Quantitative Health Sciences, and

12Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.

13Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA.

14Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

15Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France.

Address correspondence to: Martin E. Fernandez-Zapico, Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.255.0285; Email: fernandezzapico.martin@mayo.edu. Or to: Wen Wee Ma, Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.293.0487; Email: ma.wen@mayo.edu.

Find articles by Marks, D. in: JCI | PubMed | Google Scholar |

1Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, Minnesota, USA.

2Department of Gastrointestinal Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

3Division of Medical Oncology, Department of Oncology,

4Department of Pharmacology, and

5Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.

6Sanford Research, Oncology, Sanford Health, Sioux Falls, South Dakota, USA.

7Division of Hematology/Oncology, Mayo Clinic, Phoenix, Arizona, USA.

8Department of Radiology,

9Department of Laboratory Medicine and Pathology,

10Division of Epidemiology, Department of Quantitative Health Sciences,

11Division of Computational Biology, Department of Quantitative Health Sciences, and

12Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.

13Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA.

14Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

15Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France.

Address correspondence to: Martin E. Fernandez-Zapico, Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.255.0285; Email: fernandezzapico.martin@mayo.edu. Or to: Wen Wee Ma, Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.293.0487; Email: ma.wen@mayo.edu.

Find articles by Carr, R. in: JCI | PubMed | Google Scholar

1Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, Minnesota, USA.

2Department of Gastrointestinal Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

3Division of Medical Oncology, Department of Oncology,

4Department of Pharmacology, and

5Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.

6Sanford Research, Oncology, Sanford Health, Sioux Falls, South Dakota, USA.

7Division of Hematology/Oncology, Mayo Clinic, Phoenix, Arizona, USA.

8Department of Radiology,

9Department of Laboratory Medicine and Pathology,

10Division of Epidemiology, Department of Quantitative Health Sciences,

11Division of Computational Biology, Department of Quantitative Health Sciences, and

12Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.

13Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA.

14Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

15Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France.

Address correspondence to: Martin E. Fernandez-Zapico, Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.255.0285; Email: fernandezzapico.martin@mayo.edu. Or to: Wen Wee Ma, Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.293.0487; Email: ma.wen@mayo.edu.

Find articles by Toruner, M. in: JCI | PubMed | Google Scholar

1Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, Minnesota, USA.

2Department of Gastrointestinal Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

3Division of Medical Oncology, Department of Oncology,

4Department of Pharmacology, and

5Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.

6Sanford Research, Oncology, Sanford Health, Sioux Falls, South Dakota, USA.

7Division of Hematology/Oncology, Mayo Clinic, Phoenix, Arizona, USA.

8Department of Radiology,

9Department of Laboratory Medicine and Pathology,

10Division of Epidemiology, Department of Quantitative Health Sciences,

11Division of Computational Biology, Department of Quantitative Health Sciences, and

12Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.

13Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA.

14Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

15Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France.

Address correspondence to: Martin E. Fernandez-Zapico, Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.255.0285; Email: fernandezzapico.martin@mayo.edu. Or to: Wen Wee Ma, Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.293.0487; Email: ma.wen@mayo.edu.

Find articles by Sigafoos, A. in: JCI | PubMed | Google Scholar |

1Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, Minnesota, USA.

2Department of Gastrointestinal Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

3Division of Medical Oncology, Department of Oncology,

4Department of Pharmacology, and

5Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.

6Sanford Research, Oncology, Sanford Health, Sioux Falls, South Dakota, USA.

7Division of Hematology/Oncology, Mayo Clinic, Phoenix, Arizona, USA.

8Department of Radiology,

9Department of Laboratory Medicine and Pathology,

10Division of Epidemiology, Department of Quantitative Health Sciences,

11Division of Computational Biology, Department of Quantitative Health Sciences, and

12Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.

13Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA.

14Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

15Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France.

Address correspondence to: Martin E. Fernandez-Zapico, Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.255.0285; Email: fernandezzapico.martin@mayo.edu. Or to: Wen Wee Ma, Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.293.0487; Email: ma.wen@mayo.edu.

Find articles by Koenig-Kappes, A. in: JCI | PubMed | Google Scholar

1Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, Minnesota, USA.

2Department of Gastrointestinal Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

3Division of Medical Oncology, Department of Oncology,

4Department of Pharmacology, and

5Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.

6Sanford Research, Oncology, Sanford Health, Sioux Falls, South Dakota, USA.

7Division of Hematology/Oncology, Mayo Clinic, Phoenix, Arizona, USA.

8Department of Radiology,

9Department of Laboratory Medicine and Pathology,

10Division of Epidemiology, Department of Quantitative Health Sciences,

11Division of Computational Biology, Department of Quantitative Health Sciences, and

12Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.

13Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA.

14Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

15Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France.

Address correspondence to: Martin E. Fernandez-Zapico, Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.255.0285; Email: fernandezzapico.martin@mayo.edu. Or to: Wen Wee Ma, Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.293.0487; Email: ma.wen@mayo.edu.

Find articles by Olson, R. in: JCI | PubMed | Google Scholar

1Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, Minnesota, USA.

2Department of Gastrointestinal Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

3Division of Medical Oncology, Department of Oncology,

4Department of Pharmacology, and

5Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.

6Sanford Research, Oncology, Sanford Health, Sioux Falls, South Dakota, USA.

7Division of Hematology/Oncology, Mayo Clinic, Phoenix, Arizona, USA.

8Department of Radiology,

9Department of Laboratory Medicine and Pathology,

10Division of Epidemiology, Department of Quantitative Health Sciences,

11Division of Computational Biology, Department of Quantitative Health Sciences, and

12Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.

13Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA.

14Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

15Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France.

Address correspondence to: Martin E. Fernandez-Zapico, Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.255.0285; Email: fernandezzapico.martin@mayo.edu. Or to: Wen Wee Ma, Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.293.0487; Email: ma.wen@mayo.edu.

Find articles by Tolosa, E. in: JCI | PubMed | Google Scholar |

1Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, Minnesota, USA.

2Department of Gastrointestinal Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

3Division of Medical Oncology, Department of Oncology,

4Department of Pharmacology, and

5Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.

6Sanford Research, Oncology, Sanford Health, Sioux Falls, South Dakota, USA.

7Division of Hematology/Oncology, Mayo Clinic, Phoenix, Arizona, USA.

8Department of Radiology,

9Department of Laboratory Medicine and Pathology,

10Division of Epidemiology, Department of Quantitative Health Sciences,

11Division of Computational Biology, Department of Quantitative Health Sciences, and

12Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.

13Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA.

14Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

15Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France.

Address correspondence to: Martin E. Fernandez-Zapico, Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.255.0285; Email: fernandezzapico.martin@mayo.edu. Or to: Wen Wee Ma, Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.293.0487; Email: ma.wen@mayo.edu.

Find articles by Zhang, C. in: JCI | PubMed | Google Scholar |

1Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, Minnesota, USA.

2Department of Gastrointestinal Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

3Division of Medical Oncology, Department of Oncology,

4Department of Pharmacology, and

5Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.

6Sanford Research, Oncology, Sanford Health, Sioux Falls, South Dakota, USA.

7Division of Hematology/Oncology, Mayo Clinic, Phoenix, Arizona, USA.

8Department of Radiology,

9Department of Laboratory Medicine and Pathology,

10Division of Epidemiology, Department of Quantitative Health Sciences,

11Division of Computational Biology, Department of Quantitative Health Sciences, and

12Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.

13Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA.

14Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

15Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France.

Address correspondence to: Martin E. Fernandez-Zapico, Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.255.0285; Email: fernandezzapico.martin@mayo.edu. Or to: Wen Wee Ma, Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.293.0487; Email: ma.wen@mayo.edu.

Find articles by Li, H. in: JCI | PubMed | Google Scholar |

1Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, Minnesota, USA.

2Department of Gastrointestinal Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

3Division of Medical Oncology, Department of Oncology,

4Department of Pharmacology, and

5Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.

6Sanford Research, Oncology, Sanford Health, Sioux Falls, South Dakota, USA.

7Division of Hematology/Oncology, Mayo Clinic, Phoenix, Arizona, USA.

8Department of Radiology,

9Department of Laboratory Medicine and Pathology,

10Division of Epidemiology, Department of Quantitative Health Sciences,

11Division of Computational Biology, Department of Quantitative Health Sciences, and

12Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.

13Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA.

14Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

15Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France.

Address correspondence to: Martin E. Fernandez-Zapico, Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.255.0285; Email: fernandezzapico.martin@mayo.edu. Or to: Wen Wee Ma, Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.293.0487; Email: ma.wen@mayo.edu.

Find articles by Doles, J. in: JCI | PubMed | Google Scholar |

1Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, Minnesota, USA.

2Department of Gastrointestinal Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

3Division of Medical Oncology, Department of Oncology,

4Department of Pharmacology, and

5Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.

6Sanford Research, Oncology, Sanford Health, Sioux Falls, South Dakota, USA.

7Division of Hematology/Oncology, Mayo Clinic, Phoenix, Arizona, USA.

8Department of Radiology,

9Department of Laboratory Medicine and Pathology,

10Division of Epidemiology, Department of Quantitative Health Sciences,

11Division of Computational Biology, Department of Quantitative Health Sciences, and

12Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.

13Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA.

14Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

15Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France.

Address correspondence to: Martin E. Fernandez-Zapico, Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.255.0285; Email: fernandezzapico.martin@mayo.edu. Or to: Wen Wee Ma, Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.293.0487; Email: ma.wen@mayo.edu.

Find articles by Bleeker, J. in: JCI | PubMed | Google Scholar |

1Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, Minnesota, USA.

2Department of Gastrointestinal Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

3Division of Medical Oncology, Department of Oncology,

4Department of Pharmacology, and

5Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.

6Sanford Research, Oncology, Sanford Health, Sioux Falls, South Dakota, USA.

7Division of Hematology/Oncology, Mayo Clinic, Phoenix, Arizona, USA.

8Department of Radiology,

9Department of Laboratory Medicine and Pathology,

10Division of Epidemiology, Department of Quantitative Health Sciences,

11Division of Computational Biology, Department of Quantitative Health Sciences, and

12Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.

13Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA.

14Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

15Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France.

Address correspondence to: Martin E. Fernandez-Zapico, Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.255.0285; Email: fernandezzapico.martin@mayo.edu. Or to: Wen Wee Ma, Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA. Phone: 507.293.0487; Email: ma.wen@mayo.edu.

Find articles by Barrett, M. in:

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