Blocking angiogenesis represents a fundamental process in Colorectal Cancer (CRC)
treatment. VEGF (vascular endothelial growth factor) pathway is implicated in various processes
that regulate tumor vascularization and proliferation. In the last years, great efforts have been
made thanks to the discovery of targeted drugs that block VEGF and its receptors conferring a
benefit in a variety of tumors, including CRC. To date, four drugs have been approved for the
treatment of metastatic CRC (mCRC): bevacizumab, aflibercept, ramucirumab and regorafenib.
Unfortunately, patients relapse due to the appearance of resistance. The VEGF family, its role in
the angiogenesis and complex heterogeneity of mechanisms that escape tumor blockade are not
completely understood and there is a lack of biomarkers of response to anti-angiogenic drugs. We
describe the principal mechanisms of resistance to anti-VEGF therapy and discuss potential biomarkers
to be investigated in the near future.
Keywords: Colorectal cancer, angiogenesis, resistance, VEGF, biomarkers, targeted therapy.
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