A Chemosensitivity Study of Colorectal Cancer Using Xenografts of Patient-Derived Tumor-Initiating Cells.

作者: Hisatsugu Maekawa , Hiroyuki Miyoshi , Tadayoshi Yamaura , Yoshiro Itatani , Kenji Kawada

DOI: 10.1158/1535-7163.MCT-18-0128

关键词: NeoplasmFOLFIRICancer stem cellFOLFOXRegimenInternal medicineMedicineOncologyColorectal cancerChemotherapyCancer

摘要: Current genomic and gene expression analyses provide versatile tools to improve cancer chemotherapy. However, it is still difficult predict whether each patient responds a particular regimen or not. To chemosensitivity in with colorectal cancer, we developed an evaluation method using the primary tumor-initiating cells (TIC, aka stem cells) xenografted nude mice subcutaneously (patient-derived spheroid xenografts; PDSX). Simultaneously, also prepared conventional patient-derived xenografts (PDX) from same patients' tumors compared dosing results those of PDSXs. We further chemosensitivities PDSXs 7 patients who had been given regimens such as FOLFOX FOLFIRI treat their metastatic lesions. As per results, PDSX provided much more precise predictable tumor growth less variance than PDX, although both retained epithelial characteristics tumors. Likewise, drug-dosing tests showed essentially PDXs PDSXs, stronger statistical power Notably, was precisely reflected that along clinical course until resistance emerged at terminal stage. This "paraclinical" xenograft trials may help selection chemotherapy efficacious for patient, and, importantly, avoiding inefficient ones by which can lose precious time QOL. Furthermore, be employed evaluations off-label uses chemotherapeutics compassionate yet-unapproved new drugs personalized therapies. Mol Cancer Ther; 17(10); 2187-96. ©2018 AACR.

参考文章(33)
Edward A. Sausville, Preclinical Models for Anticancer Drug Development Springer, New York, NY. pp. 89- 114 ,(2011) , 10.1007/978-1-4419-7358-0_4
Bo Young Oh, Woo Yong Lee, Sungwon Jung, Hye Kyung Hong, Do-Hyun Nam, Yoon Ah Park, Jung Wook Huh, Seong Hyeon Yun, Hee Cheol Kim, Ho-Kyung Chun, Yong Beom Cho, Correlation between tumor engraftment in patient-derived xenograft models and clinical outcomes in colorectal cancer patients Oncotarget. ,vol. 6, pp. 16059- 16068 ,(2015) , 10.18632/ONCOTARGET.3863
Justin Stebbing, Keren Paz, Gary K. Schwartz, Leonard H. Wexler, Robert Maki, Raphael E. Pollock, Ronnie Morris, Richard Cohen, Arjun Shankar, Glen Blackman, Victoria Harding, David Vasquez, Jonathan Krell, Daniel Ciznadija, Amanda Katz, David Sidransky, Patient-derived xenografts for individualized care in advanced sarcoma Cancer. ,vol. 120, pp. 2006- 2015 ,(2014) , 10.1002/CNCR.28696
Marc van de Wetering, Hayley E. Francies, Joshua M. Francis, Gergana Bounova, Francesco Iorio, Apollo Pronk, Winan van Houdt, Joost van Gorp, Amaro Taylor-Weiner, Lennart Kester, Anne McLaren-Douglas, Joyce Blokker, Sridevi Jaksani, Sina Bartfeld, Richard Volckman, Peter van Sluis, Vivian S.W. Li, Sara Seepo, Chandra Sekhar Pedamallu, Kristian Cibulskis, Scott L. Carter, Aaron McKenna, Michael S. Lawrence, Lee Lichtenstein, Chip Stewart, Jan Koster, Rogier Versteeg, Alexander van Oudenaarden, Julio Saez-Rodriguez, Robert G.J. Vries, Gad Getz, Lodewyk Wessels, Michael R. Stratton, Ultan McDermott, Matthew Meyerson, Mathew J. Garnett, Hans Clevers, Prospective Derivation of a Living Organoid Biobank of Colorectal Cancer Patients Cell. ,vol. 161, pp. 933- 945 ,(2015) , 10.1016/J.CELL.2015.03.053
Jianrong Wu, Statistical Inference for Tumor Growth Inhibition T/C Ratio Journal of Biopharmaceutical Statistics. ,vol. 20, pp. 954- 964 ,(2010) , 10.1080/10543401003618983
Stephen Yiu Chuen Choi, Dong Lin, Peter W. Gout, Colin C. Collins, Yong Xu, Yuzhuo Wang, Lessons from patient-derived xenografts for better in vitro modeling of human cancer. Advanced Drug Delivery Reviews. ,vol. 79, pp. 222- 237 ,(2014) , 10.1016/J.ADDR.2014.09.009
Christopher L Morton, Peter J Houghton, Establishment of human tumor xenografts in immunodeficient mice. Nature Protocols. ,vol. 2, pp. 247- 250 ,(2007) , 10.1038/NPROT.2007.25
I. Fichtner, W. Slisow, J. Gill, M. Becker, B. Elbe, T. Hillebrand, M. Bibby, Anticancer drug response and expression of molecular markers in early-passage xenotransplanted colon carcinomas. European Journal of Cancer. ,vol. 40, pp. 298- 307 ,(2004) , 10.1016/J.EJCA.2003.10.011
F. Y. Lee, F. R. Luo, Z. Yang, H. Dong, A. Camuso, K. McGlinchey, K. Fager, C. Flefleh, D. Kan, I. Inigo, S. Castaneda, W. C. Rose, R. A. Kramer, R. Wild, Correlation of pharmacokinetics with the antitumor activity of Cetuximab in nude mice bearing the GEO human colon carcinoma xenograft Cancer Chemotherapy and Pharmacology. ,vol. 56, pp. 455- 464 ,(2005) , 10.1007/S00280-005-1022-3
J. Kondo, H. Endo, H. Okuyama, O. Ishikawa, H. Iishi, M. Tsujii, M. Ohue, M. Inoue, Retaining cell–cell contact enables preparation and culture of spheroids composed of pure primary cancer cells from colorectal cancer Proceedings of the National Academy of Sciences of the United States of America. ,vol. 108, pp. 6235- 6240 ,(2011) , 10.1073/PNAS.1015938108