Patient-Derived Models of Cancer in the NCI PDMC Consortium: Selection, Pitfalls, and Practical Recommendations

doi:10.3390/cancers16030565

Review

. 2024 Jan 29;16(3):565.

doi: 10.3390/cancers16030565.

Patient-Derived Models of Cancer in the NCI PDMC Consortium: Selection, Pitfalls, and Practical Recommendations

Amber N Habowski¹, Deepthi P Budagavi¹, Sandra D Scherer², Arin B Aurora³, Giuseppina Caligiuri¹, William F Flynn⁴, Ellen M Langer⁵, Jonathan R Brody⁶, Rosalie C Sears⁷, Giorgia Foggetti⁸, Anna Arnal Estape⁹, Don X Nguyen¹⁰, Katerina A Politi¹⁰, Xiling Shen¹¹, David S Hsu¹², Donna M Peehl¹³, John Kurhanewicz¹³, Renuka Sriram¹³, Milagros Suarez¹⁴, Sophie Xiao¹⁴, Yuchen Du¹⁴, Xiao-Nan Li¹⁴, Nora M Navone¹⁵, Estefania Labanca¹⁵, Christopher D Willey¹⁶

Affiliations

¹ Cold Spring Harbor Laboratory, Long Island, NY 11724, USA.
² Department of Oncologic Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
³ Children's Research Institute and Department of Pediatrics, University of Texas Southwestern, Dallas, TX 75235, USA.
⁴ Jackson Laboratory, Farmington, CT 06032, USA.
⁵ Division of Oncological Sciences, Oregon Health & Science University, Portland, OR 97239, USA.
⁶ Department of Surgery, Oregon Health & Science University, Portland, OR 97239, USA.
⁷ Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR 97239, USA.
⁸ Ospedale San Raffaele, 20054 Milano, Italy.
⁹ Department of Internal Medicine, Yale University, New Haven, CT 06520, USA.
¹⁰ Department of Pathology, Yale University, New Haven, CT 06520, USA.
¹¹ Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90024, USA.
¹² Department of Medicine, Duke University, Durham, NC 27710, USA.
¹³ Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, USA.
¹⁴ Department of Pediatrics, Lurie Children's Hospital of Chicago Northwestern University, Chicago, IL 60611, USA.
¹⁵ Department of Genitourinary Medical Oncology, David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
¹⁶ Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL 35233, USA.

PMID: 38339316
PMCID: PMC10854945
DOI: 10.3390/cancers16030565

Review

Patient-Derived Models of Cancer in the NCI PDMC Consortium: Selection, Pitfalls, and Practical Recommendations

Amber N Habowski et al. Cancers (Basel). 2024.

. 2024 Jan 29;16(3):565.

doi: 10.3390/cancers16030565.

Authors

Affiliations

¹ Cold Spring Harbor Laboratory, Long Island, NY 11724, USA.
² Department of Oncologic Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
³ Children's Research Institute and Department of Pediatrics, University of Texas Southwestern, Dallas, TX 75235, USA.
⁴ Jackson Laboratory, Farmington, CT 06032, USA.
⁵ Division of Oncological Sciences, Oregon Health & Science University, Portland, OR 97239, USA.
⁶ Department of Surgery, Oregon Health & Science University, Portland, OR 97239, USA.
⁷ Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR 97239, USA.
⁸ Ospedale San Raffaele, 20054 Milano, Italy.
⁹ Department of Internal Medicine, Yale University, New Haven, CT 06520, USA.
¹⁰ Department of Pathology, Yale University, New Haven, CT 06520, USA.
¹¹ Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90024, USA.
¹² Department of Medicine, Duke University, Durham, NC 27710, USA.
¹³ Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, USA.
¹⁴ Department of Pediatrics, Lurie Children's Hospital of Chicago Northwestern University, Chicago, IL 60611, USA.
¹⁵ Department of Genitourinary Medical Oncology, David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
¹⁶ Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL 35233, USA.

PMID: 38339316
PMCID: PMC10854945
DOI: 10.3390/cancers16030565

Abstract

For over a century, early researchers sought to study biological organisms in a laboratory setting, leading to the generation of both in vitro and in vivo model systems. Patient-derived models of cancer (PDMCs) have more recently come to the forefront of preclinical cancer models and are even finding their way into clinical practice as part of functional precision medicine programs. The PDMC Consortium, supported by the Division of Cancer Biology in the National Cancer Institute of the National Institutes of Health, seeks to understand the biological principles that govern the various PDMC behaviors, particularly in response to perturbagens, such as cancer therapeutics. Based on collective experience from the consortium groups, we provide insight regarding PDMCs established both in vitro and in vivo, with a focus on practical matters related to developing and maintaining key cancer models through a series of vignettes. Although every model has the potential to offer valuable insights, the choice of the right model should be guided by the research question. However, recognizing the inherent constraints in each model is crucial. Our objective here is to delineate the strengths and limitations of each model as established by individual vignettes. Further advances in PDMCs and the development of novel model systems will enable us to better understand human biology and improve the study of human pathology in the lab.

Keywords: metastasis; mouse models; organoids; patient derived models of cancer; sequencing; tumor cells; tumor microenvironment.

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Conflict of interest statement

The following authors declare financial interests: S.D.S. may receive royalties for PDMCs licensed by The University of Utah. R.C.S. is a consultant for Novartis and Larkspur Biosciences and on the Scientific Advisory Board of RAPPTA Therapeutics, with research funding from Cardiff Oncology and AstraZeneca. D.X.N. receives research funding from AstraZeneca. K.A.P. is a co-founder of Reveal Therapeutics; is a co-inventor for a patent for EGFRT790M mutation testing licensed to Molecular MD (through Memorial Sloan Kettering Cancer Center); is a consultant for AstraZeneca and Jannssen; and has research funding from AstraZeneca, Boehringer Ingelheim, Roche/Genentech, and D2G Oncology. X.S. is a co-founder of Xilis, Inc. and a co-inventor on patents related to micro-organospheres. S.D.H. is a co-founder of Xilis, Inc. C.D.W. is a part-time consultant for LifeNet Health and has research funding from AACR-Novocure, OMS Foundation, and Varian Medical Systems. Patent # 11,789,011 (Rosalie C. Sears, Ellen M. Langer). Title: Engineered three-dimensional breast tissue, adipose tissue, and tumor disease model. The remaining authors have no conflicts to report.

Figures

**Figure 1**
MOSs retain patient TME. (A) Tumor spheres form rapidly in MOSs. (B) scRNA-seq of MOSs developed from lung cancer tissue retains all major cell clusters, including tumor, fibroblast, lymphoid, and myeloid cells. (C) Flow cytometry shows the presence of all major immune cell populations in MOSs. (D) Immunofluorescence shows expression of T-cell markers in MOSs.

**Figure 2**
Options and considerations when selecting a PDMC. There is a diverse array of PDMCs that can be used to investigate a defined research question. PDMCs require consideration of research compliance/ethics/institute support/infrastructure that can influence model selection. Model systems are primarily split between in vitro and in vivo systems, and each has its own value and additional methodological considerations. Additional important steps include model validation, namely, quality control and credentialing (benchmarking), and eventual model sharing and publication to further advance the PDMC community and cancer biology research. Created with BioRender.com.

See this image and copyright information in PMC

References

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[1] Harrison R.G., Greenman M.J., Mall F.P., Jackson C.M. Observations of the living developing nerve fiber. Anat. Rec. 1907;1:116–128. doi: 10.1002/ar.1090010503. - DOI

[2] Harrison R.G., Greenman M.J., Mall F.P., Jackson C.M. Observations of the living developing nerve fiber. Anat. Rec. 1907;1:116–128. doi: 10.1002/ar.1090010503. - DOI

[3] Carrel A. Cultivation of adult tissues and organs outside of the body. JAMA J. Am. Med. Assoc. 1910;55:1379. doi: 10.1001/jama.1910.04330160047018. - DOI

[4] Carrel A. Cultivation of adult tissues and organs outside of the body. JAMA J. Am. Med. Assoc. 1910;55:1379. doi: 10.1001/jama.1910.04330160047018. - DOI

[5] Carrel A., Burrows M.T. Cultivation of sarcoma outside of the body. JAMA J. Am. Med. Assoc. 1910;55:1554. doi: 10.1001/jama.1910.04330180042017. - DOI

[6] Carrel A., Burrows M.T. Cultivation of sarcoma outside of the body. JAMA J. Am. Med. Assoc. 1910;55:1554. doi: 10.1001/jama.1910.04330180042017. - DOI

[7] Earle W.R. Production of malignancy in vitro. J. Natl. Cancer Inst. 1943;4:165–212.

[8] Earle W.R. Production of malignancy in vitro. J. Natl. Cancer Inst. 1943;4:165–212.

[9] Scherer W.F., Syverton J.T., Gey G.O. Studies on the propagation in vitro of poliomyelitis viruses. J. Exp. Med. 1953;97:695–710. doi: 10.1084/jem.97.5.695. - DOI - PMC - PubMed

[10] Scherer W.F., Syverton J.T., Gey G.O. Studies on the propagation in vitro of poliomyelitis viruses. J. Exp. Med. 1953;97:695–710. doi: 10.1084/jem.97.5.695. - DOI - PMC - PubMed

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Patient-Derived Models of Cancer in the NCI PDMC Consortium: Selection, Pitfalls, and Practical Recommendations

Affiliations

Patient-Derived Models of Cancer in the NCI PDMC Consortium: Selection, Pitfalls, and Practical Recommendations

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Abstract

Conflict of interest statement

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