title: Differential response to EGFR- and VEGF-targeted therapies in patient-derived             tumor tissue xenograft models of colon carcinoma and related metastases.
abstract: Heterogeneity in primary tumors and related metastases may result in failure             of antitumor therapies, particularly in targeted therapies for the treatment of             cancer. In this study, patient-derived tumor tissue (PDTT) xenograft models of             colon carcinoma with lymphatic and hepatic metastases were used to evaluate the             response to EGFR- and VEGF-targeted therapies. Our results showed that primary             colon carcinoma and its corresponding lymphatic and hepatic metastases have a             different response rate to anti-EGFR (cetuximab) and anti-VEGF (bevacizumab) therapies.             However, the underlying mechanism of these types of phenomenon is still unclear.             To investigate whether such phenomena may result from the heterogeneity in primary             colon carcinoma and related metastases, we compared the expression levels of cell             signaling pathway proteins using immunohistochemical staining and western blotting,             and the gene status of KRAS using pyrosequencing in the same primary colon carcinoma             and its corresponding lymphatic and hepatic metastatic tissues which were used             for establishing the PDTT xenograft models. Our results showed that the expression             levels of EGFR, VEGF, Akt/pAkt, ERK/pERK, MAPK/pMAPK, and mTOR/pmTOR were different             in primary colon carcinoma and matched lymphatic and hepatic metastases although             the KRAS gene status in all cases was wild-type. Our results indicate that the             heterogeneity in primary colon carcinoma and its corresponding lymphatic and hepatic             metastases may result in differences in the response to dual-inhibition of EGFR             and VEGF.
authors.affiliation: Department of Surgical Oncology, Wenzhou Medical College, Linhai, Zhejiang, People's Republic of China. jinketao2001@zju.edu.cn
authors.forename: Ketao
authors.initials: K
authors.lastname: Jin
authors.forename: Huanrong
authors.initials: H
authors.lastname: Lan
authors.forename: Feilin
authors.initials: F
authors.lastname: Cao
authors.forename: Na
authors.initials: N
authors.lastname: Han
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Xu
authors.forename: Guangliang
authors.initials: G
authors.lastname: Li
authors.forename: Kuifeng
authors.initials: K
authors.lastname: He
authors.forename: Lisong
authors.initials: L
authors.lastname: Teng
mesh_terms: D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D001483:Base Sequence; D000068258:Bevacizumab; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics / Q000556:secondary*; D000068818:Cetuximab; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000556:secondary*; D008207:Lymphatic Metastasis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D047368:Tumor Burden / Q000187:drug effects; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D018631:ras Proteins / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab