Molecular predictors of combination targeted therapies (cetuximab, bevacizumab) in irinotecan-refractory colorectal cancer (BOND-2 study) Journal Article

Authors: Zhang, W.; Azuma, M.; Lurje, G.; Gordon, M. A.; Yang, D.; Pohl, A.; Ning, Y.; Bohanes, P.; Gerger, A.; Winder, T.; Hollywood, E.; Danenberg, K. D.; Saltz, L.; Lenz, H. J.
Article Title: Molecular predictors of combination targeted therapies (cetuximab, bevacizumab) in irinotecan-refractory colorectal cancer (BOND-2 study)
Abstract: Background: To test whether intratumoral gene expression levels and germline polymorphisms predict clinical outcome in metastatic colorectal cancer (mCRC) patients treated with cetuximab and bevacizumab plus irinotecan (CBI) vs. cetuximab and bevacizumab (CB)(BOND2). Patients and Methods: Genomic DNA was extracted for genotyping from 65 patients (31: CBI arm and 34: CB arm). Thirty five patients had tissue samples available for the gene expression assay (18: CBI arm and 17: CB arm). Results: High intratumoral gene expression levels of EGFR, VEGFR2 and NRPl were associated with longer overall survival (OS) in patients receiving combined monoclonal antibodies with or without irinotecan. FCGR3A V158F, CyclinD1 A870G and EGFR R497K polymorphisms are associated with clinical outcome in patients received combined cetuximab and bevacizumab. Conclusions: Intratumoral gene expression levels of EGFR, VEGFR2 and NRP as well as polymorphisms in FCGR3A, CyclinD1 and EGFR could predict clinical outcome in mCRC patients enrolled in BOND2, independent of KRAS mutation status.
Keywords: adult; human tissue; aged; aged, 80 and over; middle aged; survival rate; young adult; gene mutation; major clinical study; overall survival; bevacizumab; cancer combination chemotherapy; outcome assessment; colorectal cancer; metastasis; gene expression; antineoplastic combined chemotherapy protocols; epidermal growth factor receptor; camptothecin; genetic association; genotype; drug resistance, neoplasm; vasculotropin receptor 2; cetuximab; cancer resistance; irinotecan; colorectal neoplasms; cd16 antigen; antibodies, monoclonal; predictive value of tests; predictor variable; oncogene k ras; cyclin d1; angiogenesis inhibitors; dna extraction; polymorphism, genetic; genomic dna; genetic polymorphism; metastatic colorectal cancer; clinical outcome; gene expression level; polymorphisms
Journal Title: Anticancer Research
Volume: 30
Issue: 10
ISSN: 0250-7005
Publisher: International Institute of Anticancer Research  
Date Published: 2010-10-01
Start Page: 4209
End Page: 4217
Language: English
PUBMED: 21036743
PROVIDER: scopus
Notes: --- - "Export Date: 20 April 2011" - "CODEN: ANTRD" - "Source: Scopus"