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A rectal cancer organoid platform to study individual responses to chemoradiation

Ganesh, Karuna ; Wu, Chao ; O'Rourke, Kevin P ; Szeglin, Bryan C ; Zheng, Youyun ; Sauvé, Charles-Etienne Gabriel ; Adileh, Mohammad ; Wasserman, Isaac ; Marco, Michael R ; Kim, Amanda S ; Shady, Maha ; Sanchez-Vega, Francisco ; Karthaus, Wouter R ; Won, Helen H ; Choi, Seo-Hyun ; Pelossof, Raphael ; Barlas, Afsar ; Ntiamoah, Peter ; Pappou, Emmanouil ; Elghouayel, Arthur ; Strong, James S ; Chen, Chin-Tung ; Harris, Jennifer W ; Weiser, Martin R ; Nash, Garrett M ; Guillem, Jose G ; 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 ; Chen, Xi ; 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

Nature medicine, 2019-10, Vol.25 (10), p.1607-1614 [Periódico revisado por pares]

United States: Nature Publishing Group

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Título:
A rectal cancer organoid platform to study individual responses to chemoradiation
Autor: Ganesh, Karuna ; Wu, Chao ; O'Rourke, Kevin P ; Szeglin, Bryan C ; Zheng, Youyun ; Sauvé, Charles-Etienne Gabriel ; Adileh, Mohammad ; Wasserman, Isaac ; Marco, Michael R ; Kim, Amanda S ; Shady, Maha ; Sanchez-Vega, Francisco ; Karthaus, Wouter R ; Won, Helen H ; Choi, Seo-Hyun ; Pelossof, Raphael ; Barlas, Afsar ; Ntiamoah, Peter ; Pappou, Emmanouil ; Elghouayel, Arthur ; Strong, James S ; Chen, Chin-Tung ; Harris, Jennifer W ; Weiser, Martin R ; Nash, Garrett M ; Guillem, Jose G ; 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 ; Chen, Xi ; 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
Assuntos: Allografts ; Animals ; Cancer ; Care and treatment ; Chemoradiotherapy ; Chemotherapy ; Clinical isolates ; Colon cancer ; Colorectal cancer ; Fluorouracil - pharmacology ; Humans ; Invasiveness ; Liver Neoplasms - drug therapy ; Liver Neoplasms - pathology ; Liver Neoplasms - radiotherapy ; Liver Neoplasms - secondary ; Liver transplantation ; Lung Neoplasms - drug therapy ; Lung Neoplasms - pathology ; Lung Neoplasms - radiotherapy ; Lung Neoplasms - secondary ; Metastases ; Mice ; Mucosa ; Neoplasm Metastasis ; Organoids ; Organoids - drug effects ; Organoids - pathology ; Organoids - radiation effects ; Patients ; Radiation ; Radiotherapy ; Rectal Neoplasms - drug therapy ; Rectal Neoplasms - pathology ; Rectal Neoplasms - radiotherapy ; Rectum ; Sensitivity ; Surgery ; Syngeneic grafts ; Tumors
É parte de: Nature medicine, 2019-10, Vol.25 (10), p.1607-1614
Notas: Equal contributions were made by K. Ganesh, C. Wu, C. L. Sawyers, and J. J. Smith.
Author Contributions
J.J.S. conceived the initial idea behind this work in concert with K.G., C.W., C.L.S., and J.G.-A., and edited/wrote the paper with K.G./C.W./B.C.S./C.L.S.. C.W., K.G., M.A., K.P.O., B.C.S., P.B.R., A.S.K., and J.J.S. performed the experiments and collected the data. J.J.S., C.W., C.L.S., B.C.S., C.-E.G.S., and K.G. made final edits, figures, and completed the paper. K.G., K.P.O., S.W.L., and L.E.D. provided the initial technical expertise to complete this work and assisted in editing the paper, along with P.B.R.. W.R.K. and H.C. provided initial expertise and critical input on the derivation of the RC tumoroids, along with critical input on the final figures and methods. P.B.R. and A.S.K. completed the radiation biology experiments. P.B.P., M.A., and R.N.K. completed initial pilot ex vivo radiation experiments that formed important preliminary data for the currently displayed radiation work. I.P., E.J.O., and H.V. made significant contributions to interpreting and gathering radiographic data and images. I.W., R.P., M.R.M., A.E., J.S.S., J.S., and B.C.S. made significant contributions to obtaining and interpreting the data from Fig. 2 and 3. M.S., Y.Z., F.S.-V., H.H.W., and R.A.P. made significant contributions relative to either obtaining or interpreting the data from Fig. 1 and Extended Data Fig. 6. S.-H.C., C.-T.C., and J.W.H. played critical roles in the collection, assessment, analysis, and execution of the experiments completed in Fig. 1, 3, and 4. J.A.L., S.P. and X.C. reviewed the data and advised the biostatistical and logistic regression aspects of this work. A.B., P.N., and K.O.M.-T. played critical roles in the characterization of the model with histopathologic and immunochemical expertise. J.S. performed the histopathologic review of tumoroid and patient H&Es. M.R.W., R.P.D., G.M.N., J.G.G., A.C., E.P., I.H.W., P.B.P., J.G.-A., L.B.S., J.M., and R.Y. contributed patients, critical clinical information, and critiqued and edited the paper. M.F.B. supervised M.S., H.H.W., and Y.Z., and conceived the MSK-IMPACT experiments and data interpretation with J.J.S.. S.W.L., J.G.-A., and C.L.S. supervised J.J.S. and provided critical input, resources, critique, and oversight of this work.
Descrição: 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.
Editor: United States: Nature Publishing Group
Idioma: Inglês

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A rectal cancer organoid platform to study individual responses to chemoradiation

United States: Nature Publishing Group

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