Abstract
Regorafenib monotherapy is a potential option for metastatic colorectal cancer patients. However, the lack of predictive factors and the severe toxicities related to treatment have made its use in clinical practice challenging. Polymorphisms of VEGF and its receptor (VEGFR) genes might regulate angiogenesis and thus potentially influence outcome during anti-angiogenesis treatment such as regorafenib. Aim of our study was to evaluate the role of VEGF and VEGFR genotyping in determining clinical outcome for colorectal cancer patients receiving regorafenib. We retrospectively collected clinical data and samples (tumour or blood) of 138 metastatic colorectal cancer patients treated with regorafenib. We analysed the correlation of different VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs) with patients’ progression-free survival (PFS) and overall survival (OS). Results from angiogenesis genotyping showed that only VEGF-A rs2010963 maintained an independent correlation with PFS and OS. Among clinical factors only ECOG PS was independently correlated with OS, whereas no correlation with PFS was evident. Grouping together those results allowed further patients stratification into 3 prognostic groups: favourable, intermediate and unfavourable. VEGF-A rs2010963 genotyping may represent an important tool for a more accurate selection of optimal candidates for regorafenib therapy.
Highlights
In the present analysis we evaluated the potential role of VEGF and VEGF receptor (VEGFR) polymorphisms in regorafenib treated colorectal cancer patients in order to define specific subgroups more likely to benefit from such a treatment approach
The capability of regorafenib to pharmacologically interact with tumour-driven angiogenesis seems to indicate that this biological pathway may be a potentially relevant predictive factor for clinical outcome during therapy
Recent analyses conducted on the cohort of patients enrolled in the CORRECT trial[16] seemed to rule out a potential predictive role of soluble serum concentrations of various factors linked to neoangiogenesis
Summary
Correspondence and requests for materials should be addressed to M.S. of evidence suggested a possible correlation between an altered expression of the angiogenetic pathway identified through polymorphisms analysis and global outcome in colorectal, gastric, breast, ovarian, renal cell and hepatocellular patients treated with drugs directed against tumour neoangiogenesis[8,9]. All known VEGF polymorphisms are not located in the coding region, different biological mechanisms in influencing gene expression and clinical outcome have been proposed[10,11]. Many molecular events leading to tumour neoangiogenesis have been linked to SNPs in the VEGF and VEGF receptor (VEGFR) genes. In the present analysis we evaluated the potential role of VEGF and VEGFR polymorphisms in regorafenib treated colorectal cancer patients in order to define specific subgroups more likely to benefit from such a treatment approach
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
