A path to translation: How 3D patient tumor avatars enable next generation precision oncology

Shree Bose¹, Margarida Barroso², Milan G Chheda³, Hans Clevers⁴, Elena Elez⁵, Salma Kaochar⁶, Scott E Kopetz⁷, Xiao-Nan Li⁸, Funda Meric-Bernstam⁹, Clifford A Meyer¹⁰, Haiwei Mou¹¹, Kristen M Naegle¹², Martin F Pera¹³, Zinaida Perova¹⁴, Katerina A Politi¹⁵, Benjamin J Raphael¹⁶, Paul Robson¹⁷, Rosalie C Sears¹⁸, Josep Tabernero⁵, David A Tuveson¹⁹, Alana L Welm²⁰, Bryan E Welm²¹, Christopher D Willey²², Konstantin Salnikow²³, Jeffrey H Chuang²⁴, Xiling Shen²⁵

Affiliations

¹ Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27708, USA.
² Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA.
³ Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110 USA.
⁴ Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center, Uppsalalaan 8, Utrecht, 3584 CT, Netherlands; Research and Early Development (pRED) of F. Hoffmann-La Roche Ltd, Roche Pharma, Basel, Switzerland.
⁵ Vall d'Hebron Hospital Campus and Institute of Oncology, International Oncology Bureau-Quiron, University of Vic-Central University of Catalonia, Barcelona, 08035 Spain.
⁶ Department of Medicine, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
⁷ The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
⁸ Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, USA.
⁹ Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
¹⁰ Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02215, USA; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27708, USA.
¹¹ The Wistar Institute, Philadelphia, PA 19104, USA.
¹² Department of Biomedical Engineering and the Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22903, USA.
¹³ The Jackson Laboratory, Bar Harbor, ME 04660, USA.
¹⁴ European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK.
¹⁵ Departments of Pathology and Internal Medicine (Medical Oncology), Yale School of Medicine and Yale Cancer Center, New Haven, CT 06510, USA.
¹⁶ Department of Computer Science, Princeton University, Princeton, NJ 08540, USA.
¹⁷ The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA; Department of Genetics and Genome Sciences, University of Connecticut School of Medicine, Farmington, CT 06032, USA; Institute for Systems Genomics, University of Connecticut, Farmington, CT 06032, USA.
¹⁸ Department of Medical and Molecular Genetics, Oregon Health & Science University, Portland, OR 97201, USA.
¹⁹ Lustgarten Foundation Pancreatic Cancer Research Laboratory at Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
²⁰ Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
²¹ Department of Surgery, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
²² Department of Radiation Oncology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
²³ Division of Cancer Biology, National Cancer Institute, NIH, Rockville, MD 20850, USA. Electronic address: salnikok@mail.nih.gov.
²⁴ The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA; Department of Genetics and Genome Sciences, University of Connecticut School of Medicine, Farmington, CT 06032, USA; Institute for Systems Genomics, University of Connecticut, Farmington, CT 06032, USA. Electronic address: jeff.chuang@jax.org.
²⁵ Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90024, USA. Electronic address: xiling.shen@terasaki.org.

PMID: 36270276
PMCID: PMC10576652
DOI: 10.1016/j.ccell.2022.09.017

A path to translation: How 3D patient tumor avatars enable next generation precision oncology

Shree Bose et al. Cancer Cell. 2022.

. 2022 Dec 12;40(12):1448-1453.

doi: 10.1016/j.ccell.2022.09.017. Epub 2022 Oct 20.

Authors

Affiliations

¹ Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27708, USA.
² Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA.
³ Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110 USA.
⁴ Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center, Uppsalalaan 8, Utrecht, 3584 CT, Netherlands; Research and Early Development (pRED) of F. Hoffmann-La Roche Ltd, Roche Pharma, Basel, Switzerland.
⁵ Vall d'Hebron Hospital Campus and Institute of Oncology, International Oncology Bureau-Quiron, University of Vic-Central University of Catalonia, Barcelona, 08035 Spain.
⁶ Department of Medicine, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
⁷ The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
⁸ Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, USA.
⁹ Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
¹⁰ Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02215, USA; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27708, USA.
¹¹ The Wistar Institute, Philadelphia, PA 19104, USA.
¹² Department of Biomedical Engineering and the Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22903, USA.
¹³ The Jackson Laboratory, Bar Harbor, ME 04660, USA.
¹⁴ European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK.
¹⁵ Departments of Pathology and Internal Medicine (Medical Oncology), Yale School of Medicine and Yale Cancer Center, New Haven, CT 06510, USA.
¹⁶ Department of Computer Science, Princeton University, Princeton, NJ 08540, USA.
¹⁷ The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA; Department of Genetics and Genome Sciences, University of Connecticut School of Medicine, Farmington, CT 06032, USA; Institute for Systems Genomics, University of Connecticut, Farmington, CT 06032, USA.
¹⁸ Department of Medical and Molecular Genetics, Oregon Health & Science University, Portland, OR 97201, USA.
¹⁹ Lustgarten Foundation Pancreatic Cancer Research Laboratory at Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
²⁰ Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
²¹ Department of Surgery, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
²² Department of Radiation Oncology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
²³ Division of Cancer Biology, National Cancer Institute, NIH, Rockville, MD 20850, USA. Electronic address: salnikok@mail.nih.gov.
²⁴ The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA; Department of Genetics and Genome Sciences, University of Connecticut School of Medicine, Farmington, CT 06032, USA; Institute for Systems Genomics, University of Connecticut, Farmington, CT 06032, USA. Electronic address: jeff.chuang@jax.org.
²⁵ Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90024, USA. Electronic address: xiling.shen@terasaki.org.

PMID: 36270276
PMCID: PMC10576652
DOI: 10.1016/j.ccell.2022.09.017

Abstract

3D patient tumor avatars (3D-PTAs) hold promise for next-generation precision medicine. Here, we describe the benefits and challenges of 3D-PTA technologies and necessary future steps to realize their potential for clinical decision making. 3D-PTAs require standardization criteria and prospective trials to establish clinical benefits. Innovative trial designs that combine omics and 3D-PTA readouts may lead to more accurate clinical predictors, and an integrated platform that combines diagnostic and therapeutic development will accelerate new treatments for patients with refractory disease.

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Conflict of interest statement

Declarations of interests S.B., M.B., H.M., Z.P., C.A.M., K.M.N., M.F.P., R.C.S., K.S. and J.H.C. have no competing interests to declare. S.E.K. is an advisor to Xilis, Inc. F.M.B. declares consulting/advisory fees from AbbVie, Aduro BioTech Inc., Alkermes, AstraZeneca, Daiichi Sankyo Co. Ltd., DebioPharm, eFFECTOR Therapeutics, F. Hoffman-La Roche Ltd., Genentech Inc., Harbinger Health, IBM Watson, Infinity Pharmaceuticals, Jackson Laboratory, Kolon Life Science, Lengo Therapeutics, OrigiMed, PACT Pharma, Parexel International, Pfizer Inc., Protai Bio Ltd, Samsung Bioepis, Seattle Genetics Inc., Tallac Therapeutics, Tyra Biosciences, Xencor, Zymeworks, Black Diamond, Biovica, Eisai, FogPharma, Immunomedics, Inflection Biosciences, Karyopharm Therapeutics, Loxo Oncology, Mersana Therapeutics, OnCusp Therapeutics, Puma Biotechnology Inc., Seattle Genetics, Sanofi, Silverback Therapeutics, Spectrum Pharmaceuticals, and Zentalis; sponsored research to her institution from Aileron Therapeutics, Inc., AstraZeneca, Bayer Healthcare Pharmaceutical, Calithera Biosciences Inc., Curis Inc., CytomX Therapeutics Inc., Daiichi Sankyo Co. Ltd., Debiopharm International, eFFECTOR Therapeutics, Genentech Inc., Guardant Health Inc., Klus Pharma, Takeda Pharmaceutical, Novartis, Puma Biotechnology Inc., and Taiho Pharmaceutical Co.; and honoraria for a speaking engagement from Chugai Biopharmaceuticals. S.K. is a consultant for FGH BioTech and has received research funding from FGH BioTech and Systems Oncology. K.A.P. is co-inventor on a patent for EGFRT790M mutation testing issued, licensed, and with royalties paid from Molecular Diagnostics/Memorial Sloan Kettering Cancer Center. She reports research funding to the institution from AstraZeneca, Roche/Genentech, Boehringer Ingelheim, and D2G Oncology and consulting for AstraZeneca and Jannssen. M.G.C. reports grants from NeoImmuneTech, as well as other support from Orbus Therapeutics, Incyte, Merck, and UpToDate outside the submitted work; in addition, M.G.C. has a patent for Zika virus strains for the treatment of glioblastoma pending. E.E.’s full disclosures are given here: www.bit.ly/3xuWMer. J.T. reports personal financial interest in form of scientific consultancy role for Array Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, Inspirna Inc, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Ona Therapeutics, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Scandion Oncology, Scorpion Therapeutics, Seattle Genetics, Servier, Sotio Biotech, Taiho, Tessa Therapeutics, and TheraMyc; and holds stocks in Oniria Therapeutics and also educational collaboration with Imedex/HMP, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education and Physicians Education Resource (PER). D.A.T. is a member of the Scientific Advisory Board and receives stock options from Leap Therapeutics, Surface Oncology, Cygnal Therapeutics, Mestag Therapeutics, and Xilis, Inc. outside the submitted work. D.A.T. is scientific co-founder of Mestag Therapeutics. D.A.T. has received research grant support from Fibrogen, Mestag, and ONO Therapeutics. D.A.T. receives grant funding from the Lustgarten Foundation, the NIH, and the Thompson Foundation. None of this work is related to the publication. No other disclosures were reported. C.D.W. is a part-time consultant for LifeNet Health and receives grant funding from AACR-Novocure and Varian Medical Systems. X.S. and H.C. are cofounders of Xilis, Inc. and inventors on patents related to organoid research and micro-organospheres. X.S. is CEO of Xilis, Inc. H.C.’s full disclosure is given here: www.uu.nl/staff/JCClevers/Additionalfunctions. M.S., B.J.R., P.R., X.L., B.E.W., and A.L.W. do not report any conflicts.

Figures

**Figure 1:**
3D-PTAs as Precision Oncology Tools. (A) Comparison of advantages and disadvantages of current patient tumor models. (B) 3D-PTAs face key barriers to for widespread adoption in clinical decision-making. (C) Paradigm to understand benefits of combinatorial or omics- vs. 3D-PTA-guided drug selection. (D) 3D-PTAs can be evaluated as functional complements to molecular tumor characterization in clinical trials and as a powerful tool for understanding tumor biology for further drug development.

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A path to translation: How 3D patient tumor avatars enable next generation precision oncology

Affiliations

A path to translation: How 3D patient tumor avatars enable next generation precision oncology

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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