A rectal cancer model establishes a platform to study individual responses to chemoradiation
| Autor: | Lukas E. Dow, Paul B. Romesser, J. Joshua Smith, Wouter R. Karthaus, Richard Kolesnick, Andrea Cercek, Ronald P. DeMatteo, Iris H Wei, Arthur E. Elghouayel, G M Nash, Katia Manova-Todorova, Julio Garcia-Aguilar, Michael F. Berger, Helen Won, Jinru Shia, Kevin P. O’Rourke, Chin-Tung Chen, Charles L. Sawyers, Martin R. Weiser, Seo-Hyun Choi, Karuna Ganesh, Yufang Zheng, James S. Strong, Jennifer W. Harris, Scott W. Lowe, Emmanouil P. Pappou, L. B. Saltz, Bryan C. Szeglin, Barlas A, Raphael Pelossof, Chao Wu, Maha Shady, Joan Massagué, Michael R. Marco, Hans Clevers, P. Paty, Isaac Wasserman, Mohammad Adileh, Jose G. Guillem, Rona Yaeger |
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| Rok vydání: | 2019 |
| Předmět: |
Oncology
0303 health sciences Chemotherapy medicine.medical_specialty Lung Colorectal cancer business.industry medicine.medical_treatment Disease medicine.disease 3. Good health Metastasis 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure Rectal mucosa 030220 oncology & carcinogenesis Internal medicine medicine Recurrent disease business Ex vivo 030304 developmental biology |
| DOI: | 10.1101/640193 |
| Popis: | 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 individual patients. We established a biorepository of 32 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 theirex vivoresponses to clinically relevant chemotherapy and radiation treatment correlate well with responses noted in individual patients’ tumors. Upon engraftment into murine rectal mucosa, human RC tumoroids gave rise to invasive rectal cancer followed by metastasis to lung and liver. Importantly, engrafted tumors closely reflected 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,in vitroplatform coupled with endoluminal propagation in animals. |
| Databáze: | OpenAIRE |
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