A rectal cancer organoid platform to study individual responses to chemoradiation

被引：388

作者：

Ganesh, Karuna ^{[1
,2
]}

Wu, Chao ^{[3
,4
]}

O'Rourke, Kevin P. ^{[5
,6
]}

Szeglin, Bryan C. ^{[4
,7
]}

Zheng, Youyun ^{[8
,9
]}

Sauve, Charles-Etienne Gabriel ^{[4
]}

Adileh, Mohammad ^{[4
]}

Wasserman, Isaac ^{[4
]}

Marco, Michael R. ^{[4
]}

Kim, Amanda S. ^{[10
]}

Shady, Maha ^{[8
,9
]}

Sanchez-Vega, Francisco ^{[4
,11
]}

Karthaus, Wouter R. ^{[3
]}

Won, Helen H. ^{[8
,9
]}

Choi, Seo-Hyun ^{[4
]}

Pelossof, Raphael ^{[4
]}

Barlas, Afsar ^{[12
]}

Ntiamoah, Peter ^{[8
]}

Pappou, Emmanouil ^{[4
]}

Elghouayel, Arthur ^{[4
]}

Strong, James S. ^{[4
]}

Chen, Chin-Tung ^{[4
]}

Harris, Jennifer W. ^{[4
]}

Weiser, Martin R. ^{[4
]}

Nash, Garrett M. ^{[4
]}

Guillem, Jose G. ^{[4
]}

Wei, Iris H. ^{[4
]}

Kolesnick, Richard N. ^{[1
]}

Veeraraghavan, Harini ^{[13
]}

Ortiz, Eduardo J. ^{[14
]}

Petkovska, Iva ^{[14
]}

Cercek, Andrea ^{[2
]}

Manova-Todorova, Katia O. ^{[12
]}

Saltz, Leonard B. ^{[2
]}

Lavery, Jessica A. ^{[15
]}

DeMatteo, Ronald P. ^{[16
]}

Massague, Joan ^{[5
]}

Paty, Philip B. ^{[4
]}

Yaeger, Rona ^{[2
]}

Chen, Xi ^{[17
]}

Patil, Sujata ^{[15
]}

Clevers, Hans ^{[18
]}

Berger, Michael F. ^{[8
,9
]}

Lowe, Scott W. ^{[5
]}

Shia, Jinru ^{[8
,19
]}

Romesser, Paul B. ^{[10
]}

Dow, Lukas E. ^{[20
]}

Garcia-Aguilar, Julio ^{[4
]}

Sawyers, Charles L. ^{[3
]}

Smith, J. Joshua ^{[3
,4
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Mol Pharmacol Program, Sloan Kettering Inst, 1275 York Ave, New York, NY 10021 USA

[2] Mem Sloan Kettering Canc Ctr, Dept Med, Gastrointestinal Oncol Serv, 1275 York Ave, New York, NY 10021 USA

[3] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, 1275 York Ave, New York, NY 10021 USA

[4] Mem Sloan Kettering Canc Ctr, Dept Surg, Colorectal Serv, 1275 York Ave, New York, NY 10021 USA

[5] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Canc Biol & Genet Program, 1275 York Ave, New York, NY 10021 USA

[6] Rockefeller Univ, Weill Cornell Med, Sloan Kettering Triinst MD PhD Program, 1230 York Ave, New York, NY 10021 USA

[7] Albert Einstein Coll Med, Bronx, NY 10467 USA

[8] Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA

[9] Mem Sloan Kettering Canc Ctr, Marie Josee & Henry R Kravis Ctr Mol Oncol, 1275 York Ave, New York, NY 10021 USA

[10] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, 1275 York Ave, New York, NY 10021 USA

[11] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, Computat Oncol Serv, New York, NY 10021 USA

[12] Mem Sloan Kettering Canc Ctr, Mol Cytol Core Facil, 1275 York Ave, New York, NY 10021 USA

[13] Mem Sloan Kettering Canc Ctr, Dept Med Phys, New York, NY 10021 USA

[14] Mem Sloan Kettering Canc Ctr, Dept Radiol, 1275 York Ave, New York, NY 10021 USA

[15] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA

[16] Hosp Univ Penn, Dept Surg, 3400 Spruce St, Philadelphia, PA 19104 USA

[17] Sylvestor Comprehens Canc Ctr, Dept Publ Hlth Sci, Miami, FL USA

[18] Univ Med Ctr, Royal Netherlands Acad Arts & Sci, Hubrecht Inst, Utrecht, Netherlands

[19] Mem Sloan Kettering Canc Ctr, Dept Pathol, Gastrointestinal Pathol, 1275 York Ave, New York, NY 10021 USA

[20] Weill Cornell Med, Weill Cornell Grad Sch Med Sci, Dept Med & Biochem, Sandra & Edward Meyer Canc Ctr, New York, NY USA

来源：

NATURE MEDICINE | 2019年 / 25卷 / 10期

基金：

美国国家卫生研究院;

关键词：

COLORECTAL-CANCER; PREOPERATIVE CHEMORADIOTHERAPY; POSTOPERATIVE CHEMOTHERAPY; NEOADJUVANT CHEMOTHERAPY; GERMAN CAO/ARO/AIO-04; TRANSPLANTATION; FLUOROURACIL; MULTICENTER; OXALIPLATIN; THERAPY;

D O I：

10.1038/s41591-019-0584-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1607 / +

页数：22

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