VEGFA and cancer: Abnormally increased levels of angiopoietin-2 have been noticed in a wide range of cancers, including CRC, and are associated with resistance to bevacizumab.218 Targeting both VEGF and angiopoietin-2 in preclinical studies helped control proliferation and progression in cancers that were resistant to VEGF-targeted therapies.219–221 The VEGF-A and angiopoietin-2 cotargeting agent vanucizumab, which inhibited growth in a CRC xenograft model,222 has passed through a phase I study with acceptable safety and encouraging anticancer effects.223