The VEGF family in cancer and antibody-based strategies for their inhibition

Abstract

Angiogenesis is required in normal physiological processes, but is also involved in tumor growth, progression and metastasis. Vascular endothelial growth factor (VEGF), a primary mediator of angiogenesis in normal physiology and in disease, and other VEGF family members and their receptors provide targets that have been explored extensively for cancer therapy. Small molecule inhibitors and antibody/protein-based strategies that target the VEGF pathway have been studied in multiple types of cancer. This review will focus on VEGF pathway targeting antibodies that are currently being evaluated in pre-clinical and clinical studies.

Figure 1

Blockade of the VEGF pathway with mAbs. The specificity of the VEGF family ligands for the VEGF receptors and coreceptors are shown. The clinically-relevant mAbs targeting the anti-VEGF pathway discussed in this review are placed based on their blockade of VEGF ligand or receptor. The ligand-binding antibodies bevacizumab (bev), r84, and VEGF-Trap inhibit ligand binding to the indicated receptor. IMC-18F1 and IMC-1121B bind VEGFR1 and VEGFR2 respectively, and prevent ligand binding.

Figure 2

Current anti-angiogenic mAbs with applications in cancer therapy. hz, humanized; hu, human; ms, mouse; rt, rat; fp, fusion protein; mCRC, metastatic colorectal cancer; NSCLC, non-small cell lung cancer; mBC, metastatic breast cancer; mRCC, metastatic renal cell carcinoma.