美国斯隆·凯特琳纪念癌症中心J. Joshua Smith和Charles L. Sawyers课题组合作，开发出一个用于研究放化疗个体反应的直肠癌（RC）类器官平台。这一成果于2019年10月7日在线发表于《自然—医学》。

他们建立了一个来自65例原发性、转移性或复发性疾病患者的RC类器官培养物（类瘤）的生物库。RC类瘤保留了其起源肿瘤的分子特征，其对临床相关化学疗法和放射治疗的离体反应与个别患者肿瘤中显示的临床反应相关。植入鼠的直肠黏膜后，人RC类瘤产生了浸润性RC，随后转移到肺和肝。重要的是，植入的肿瘤表现出对临床观察到的化学疗法的异质敏感性。

因此，可以使用基于类器官的离体平台，结合在动物体内的腔内传播，有效地研究RC临床分离株的生物学和药物敏感性。

据悉，RC是一种具有挑战性的疾病，需要化学疗法、放射疗法和手术治疗才能优化单个患者的预后。目前没有精确的RC模型可以回答与患者相关的基础性研究问题。

附：英文原文

Title: A rectal cancer organoid platform to study individual responses to chemoradiation

Author: Karuna Ganesh, Chao Wu, Kevin P. ORourke, Bryan C. Szeglin, Youyun Zheng, Charles-Etienne Gabriel Sauv, 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 Massagu, 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

Issue&Volume: 2019-10-07

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.

DOI: 10.1038/s41591-019-0584-2

Source:https://www.nature.com/articles/s41591-019-0584-2