and Gene Polymorphisms as Predictors of Clinical Outcome to First-Line Bevacizumab-Based Treatment in Metastatic Colorectal Cancer.

Bevacizumab is used to treat metastatic colorectal cancer (mCRC). However, there are still no available predictors of clinical outcomes. We investigated selected single nucleotide polymorphisms (SNPs) in the genes involved in VEGF-dependent and -independent angiogenesis pathways and other major intracellular signaling pathways involved in the pathogenesis of mCRC as an attempt to find predictors of clinical outcome. Forty-six patients treated with first-line bevacizumab-based chemotherapy were included in this study with a 5 year follow up. Genomic DNA was isolated from whole blood for the analysis of (rs2010963, 1570360, rs699947), (rs5498, rs1799969) SNPs and from tumor tissue for the detection of genomic variants in , , genes. PCR and next generation sequencing were used for the analysis. The endpoints of the study were progression-free survival (PFS) and overall survival (OS). The rs699947 A/A allele was associated with increased PFS ( = 0.006) and OS ( = 0.043). The rs1799969 G/A allele was associated with prolonged OS ( = 0.036). Finally, wild type was associated with increased OS ( = 0.027). We identified and variants in angiogenesis and other major intracellular signaling pathways, such as , that can predict clinical outcome upon bevacizumab administration. These identified biomarkers could be used to select patients with mCRC who may achieve long-term responses and benefit from bevacizumab-based therapies.