A rectal cancer organoid platform to study individual responses to chemoradiation

Karuna Ganesh; Chao Wu; Kevin P O'Rourke; Bryan C Szeglin; Youyun Zheng; Charles-Etienne Gabriel Sauvé; Mohammad Adileh; Isaac Wasserman; Michael R Marco; Amanda S Kim; Maha Shady; Francisco Sanchez-Vega; Wouter R Karthaus; Helen H Won; Seo-Hyun Choi; Raphael Pelossof; Afsar Barlas; Peter Ntiamoah; Emmanouil Pappou; Arthur Elghouayel; James S Strong; Chin-Tung Chen; Jennifer W Harris; Martin R Weiser; Garrett M Nash; Jose G Guillem; Iris H Wei; Richard N Kolesnick; Harini Veeraraghavan; Eduardo J Ortiz; Iva Petkovska; Andrea Cercek; Katia O Manova-Todorova; Leonard B Saltz; Jessica A Lavery; Ronald P DeMatteo; Joan Massagué; Philip B Paty; Rona Yaeger; Xi Chen; Sujata Patil; Hans Clevers; Michael F Berger; Scott W Lowe; Jinru Shia; Paul B Romesser; Lukas E Dow; Julio Garcia-Aguilar; Charles L Sawyers; J Joshua Smith

doi:10.1038/s41591-019-0584-2

A rectal cancer organoid platform to study individual responses to chemoradiation

Karuna Ganesh, Chao Wu, Kevin P O'Rourke, Bryan C Szeglin, Youyun Zheng, Charles-Etienne Gabriel Sauvé, Mohammad Adileh, Isaac Wasserman, Michael R Marco, Amanda S Kim, Maha Shady, Francisco Sanchez-Vega, Wouter R Karthaus, Helen H Won, Seo-Hyun Choi, Raphael Pelossof, Afsar Barlas, Peter Ntiamoah, Emmanouil Pappou, Arthur ElghouayelJames S Strong, Chin-Tung Chen, Jennifer W Harris, Martin R Weiser, Garrett M Nash, Jose G Guillem, Iris H Wei, Richard N Kolesnick, Harini Veeraraghavan, Eduardo J Ortiz, Iva Petkovska, Andrea Cercek, Katia O Manova-Todorova, Leonard B Saltz, Jessica A Lavery, Ronald P DeMatteo, Joan Massagué, Philip B Paty, Rona Yaeger, Xi Chen, Sujata Patil, Hans Clevers, Michael F Berger, Scott W Lowe, Jinru Shia, Paul B Romesser, Lukas E Dow, Julio Garcia-Aguilar, Charles L Sawyers, J Joshua Smith

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

382 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1607-1614
Number of pages	8
Journal	Nature Medicine
Volume	25
Issue number	10
DOIs	https://doi.org/10.1038/s41591-019-0584-2
Publication status	Published - Oct 2019

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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., ... Smith, J. J. (2019). A rectal cancer organoid platform to study individual responses to chemoradiation. Nature Medicine, 25(10), 1607-1614. https://doi.org/10.1038/s41591-019-0584-2

@article{946f1b8d14a549f3a93c23d4a6b4278d,

title = "A rectal cancer organoid platform to study individual responses to chemoradiation",

abstract = "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.",

author = "Karuna Ganesh and Chao Wu and O'Rourke, {Kevin P} and Szeglin, {Bryan C} and Youyun Zheng and Sauv{\'e}, {Charles-Etienne Gabriel} and Mohammad Adileh and Isaac Wasserman and Marco, {Michael R} and Kim, {Amanda S} and Maha Shady and Francisco Sanchez-Vega and Karthaus, {Wouter R} and Won, {Helen H} and Seo-Hyun Choi and Raphael Pelossof and Afsar Barlas and Peter Ntiamoah and Emmanouil Pappou and Arthur Elghouayel and Strong, {James S} and Chin-Tung Chen and Harris, {Jennifer W} and Weiser, {Martin R} and Nash, {Garrett M} and Guillem, {Jose G} and Wei, {Iris H} and Kolesnick, {Richard N} and Harini Veeraraghavan and Ortiz, {Eduardo J} and Iva Petkovska and Andrea Cercek and Manova-Todorova, {Katia O} and Saltz, {Leonard B} and Lavery, {Jessica A} and DeMatteo, {Ronald P} and Joan Massagu{\'e} and Paty, {Philip B} and Rona Yaeger and Xi Chen and Sujata Patil and Hans Clevers and Berger, {Michael F} and Lowe, {Scott W} and Jinru Shia and Romesser, {Paul B} and Dow, {Lukas E} and Julio Garcia-Aguilar and Sawyers, {Charles L} and Smith, {J Joshua}",

year = "2019",

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doi = "10.1038/s41591-019-0584-2",

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volume = "25",

pages = "1607--1614",

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Ganesh, K, Wu, C, O'Rourke, KP, Szeglin, BC, Zheng, Y, Sauvé, C-EG, Adileh, M, Wasserman, I, Marco, MR, Kim, AS, Shady, M, Sanchez-Vega, F, Karthaus, WR, Won, HH, Choi, S-H, Pelossof, R, Barlas, A, Ntiamoah, P, Pappou, E, Elghouayel, A, Strong, JS, Chen, C-T, Harris, JW, Weiser, MR, Nash, GM, Guillem, JG, Wei, IH, Kolesnick, RN, Veeraraghavan, H, Ortiz, EJ, Petkovska, I, Cercek, A, Manova-Todorova, KO, Saltz, LB, Lavery, JA, DeMatteo, RP, Massagué, J, Paty, PB, Yaeger, R, Chen, X, Patil, S, Clevers, H, Berger, MF, Lowe, SW, Shia, J, Romesser, PB, Dow, LE, Garcia-Aguilar, J, Sawyers, CL & Smith, JJ 2019, 'A rectal cancer organoid platform to study individual responses to chemoradiation', Nature Medicine, vol. 25, no. 10, pp. 1607-1614. https://doi.org/10.1038/s41591-019-0584-2

TY - JOUR

T1 - A rectal cancer organoid platform to study individual responses to chemoradiation

AU - Ganesh, Karuna

AU - Wu, Chao

AU - O'Rourke, Kevin P

AU - Szeglin, Bryan C

AU - Zheng, Youyun

AU - Sauvé, Charles-Etienne Gabriel

AU - Adileh, Mohammad

AU - Wasserman, Isaac

AU - Marco, Michael R

AU - Kim, Amanda S

AU - Shady, Maha

AU - Sanchez-Vega, Francisco

AU - Karthaus, Wouter R

AU - Won, Helen H

AU - Choi, Seo-Hyun

AU - Pelossof, Raphael

AU - Barlas, Afsar

AU - Ntiamoah, Peter

AU - Pappou, Emmanouil

AU - Elghouayel, Arthur

AU - Strong, James S

AU - Chen, Chin-Tung

AU - Harris, Jennifer W

AU - Weiser, Martin R

AU - Nash, Garrett M

AU - Guillem, Jose G

AU - Wei, Iris H

AU - Kolesnick, Richard N

AU - Veeraraghavan, Harini

AU - Ortiz, Eduardo J

AU - Petkovska, Iva

AU - Cercek, Andrea

AU - Manova-Todorova, Katia O

AU - Saltz, Leonard B

AU - Lavery, Jessica A

AU - DeMatteo, Ronald P

AU - Massagué, Joan

AU - Paty, Philip B

AU - Yaeger, Rona

AU - Chen, Xi

AU - Patil, Sujata

AU - Clevers, Hans

AU - Berger, Michael F

AU - Lowe, Scott W

AU - Shia, Jinru

AU - Romesser, Paul B

AU - Dow, Lukas E

AU - Garcia-Aguilar, Julio

AU - Sawyers, Charles L

AU - Smith, J Joshua

PY - 2019/10

Y1 - 2019/10

N2 - 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.

AB - 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.

U2 - 10.1038/s41591-019-0584-2

DO - 10.1038/s41591-019-0584-2

M3 - Article

C2 - 31591597

SN - 1078-8956

VL - 25

SP - 1607

EP - 1614

JO - Nature Medicine

JF - Nature Medicine

IS - 10

ER -

A rectal cancer organoid platform to study individual responses to chemoradiation

Abstract

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