A rectal cancer organoid platform to study individual responses to chemoradiation
Open accessAbstract
Rectal cancer (RC) is a challenging disease to treat that requires chemotherapy, radiation and surgery to optimize outcomes for individual patients. No accurate model of RC exists to answer fundamental research questions relevant to patients. We established a biorepository of 65 patient-derived RC organoid cultures (tumoroids) from patients with primary, metastatic or recurrent disease. RC tumoroids retained molecular features of the tumors from which they were derived, and their ex vivo responses to clinically relevant chemotherapy and radiation treatment correlated with the clinical responses noted in individual patients' tumors. Upon engraftment into murine rectal mucosa, human RC tumoroids gave rise to invasive RC followed by metastasis to lung and liver. Importantly, engrafted tumors displayed the heterogenous sensitivity to chemotherapy observed clinically. Thus, the biology and drug sensitivity of RC clinical isolates can be efficiently interrogated using an organoid-based, ex vivo platform coupled with in vivo endoluminal propagation in animals.
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Patient-derived tumoroid models show promise in testing drug efficacy and potentially determining a personalized treatment for the patient.
“patient-derived tumoroid models also show promise in testing drug efficacy and potentially determining a personalized treatment for the patient7–12.”
From One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids (2023) · cites this paper as [8]
PDOs have emerged as a promising preclinical model for therapeutic prediction and functional studies across multiple cancer types, including in PDAC.
“PDOs have emerged as a promising preclinical model for therapeutic prediction and functional studies across multiple cancer types, including in PDAC18,19,48–50.”
From Occult polyclonality of preclinical pancreatic cancer models drives in vitro evolution (2022) · cites this paper as [49]
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- Authors
- Ganesh, K., Wu, C., O’Rourke, K. P., Szeglin, B. C., Zheng, Y., Sauvé, C.-E. G., Adileh, M., Wasserman, I., Marco, M. R., Kim, A. S., Shady, M., Sanchez-Vega, F., Karthaus, W. R., Won, H. H., Choi, S.-H., Pelossof, R., Barlas, A., Ntiamoah, P., Pappou, E., Elghouayel, A., Strong, J. S., Chen, C.-T., Harris, J. W., Weiser, M. R., Nash, G. M., Guillem, J. G., Wei, I. H., Kolesnick, R. N., Veeraraghavan, H., Ortiz, E. J., Petkovska, I., Cercek, A., Manova-Todorova, K. O., Saltz, L. B., Lavery, J. A., DeMatteo, R. P., Massagué, J., Paty, P. B., Yaeger, R., Chen, X., Patil, S., Clevers, H., Berger, M. F., Lowe, S. W., Shia, J., Romesser, P. B., Dow, L. E., Garcia-Aguilar, J., Sawyers, C. L., & Smith, J. J.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Albert Einstein College of Medicine (US)
- Hospital of the University of Pennsylvania (US)
- Sylvester Comprehensive Cancer Center (US)
- Royal Netherlands Academy of Arts and Sciences (NL)
- Weill Cornell Medicine (US)
- Corresponding author
- Sawyers, Charles L.
- Smith, J. Joshua
- ORCID
- Ganesh, Karuna
- Wu, Chao
- Szeglin, Bryan C.
- Zheng, Youyun
- Sauvé, Charles-Etienne Gabriel
- Wasserman, Isaac
- Marco, Michael R.
- Shady, Maha
- Karthaus, Wouter R.
- Won, Helen H.
- Choi, Seo-Hyun
- Ntiamoah, Peter
- Pappou, Emmanouil
- Chen, Chin-Tung
- Weiser, Martin R.
- Nash, Garrett M.
- Wei, Iris H.
- Kolesnick, Richard N.
- Veeraraghavan, Harini
- Ortiz, Eduardo J.
- Petkovska, Iva
- Cercek, Andrea
- Manova-Todorova, Katia O.
- Saltz, Leonard B.
- Lavery, Jessica A.
- DeMatteo, Ronald P.
- Massagué, Joan
- Paty, Philip B.
- Yaeger, Rona
- Patil, Sujata
- Clevers, Hans
- Berger, Michael F.
- Lowe, Scott W.
- Shia, Jinru
- Romesser, Paul B.
- Dow, Lukas E.
- Garcia-Aguilar, Julio
- Sawyers, Charles L.
- Smith, J. Joshua
- Venue
- Nature Medicine
- Published
- 2019-10
- Volume
- 25
- Issue
- 10
- Pages
- 1607-1614
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC7385919
- OpenAlex
- W2978373708
- Cited by
- 569
- References
- 45
- Citations by year
- 2026: 65 · 2025: 90 · 2024: 89 · 2023: 81 · 2022: 100 · 2021: 98 · 2020: 40 · 2019: 6
- FWCI
- 25.46
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (submittedVersion)
- Funders
- National Institutes of Health (5u54ca224079-04, U54OD020355, TL1TR002386)
- National Cancer Institute (T32CA160001, K22CA181280, U54-CA224079, P01CA129243, P01CA094060, F30CA200110, R01CA182551, K08CA230213, R01CA155169, P30CA008748, K12CA184746, T32CA009207, P50CA092629, R25CA020449, R01CA193837)
- National Institute of General Medical Sciences (T32GM007739)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Keywords
- rectal cancer, tumor organoids, chemoradiotherapy, drug sensitivity, patient-derived organoids, biorepository, metastasis, lung metastasis, liver metastasis, chemoresistance, prediction model
- MeSH terms
- Animals, Fluorouracil, Humans, Liver Neoplasms, Lung Neoplasms, Neoplasm Metastasis, Organoids, Rectal Neoplasms, Mice, Chemoradiotherapy
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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