Angiogenesis Inhibitors

Abstract

Angiogenesis, the formation of new capillary blood vessels from preexisting vasculature, plays an essential role in organ growth and wound repair. However, pathological angiogenesis is a hallmark of various cancers and a range of nonneoplastic diseases including ischaemic and inflammatory disorders. Angiogenesis is a complicated multistep process that precisely mediated by the balance between pro‐ and antiangiogenic factors. Concentrated efforts in this area of research have led to the discovery of a growing number of angiogenesis‐related molecules and the complex interactions among these molecules. The integrated understanding of molecular mechanism of angiogenesis process involved in tumor growth and metastasis has identified angiogenesis as a promising target for cancer therapy. Over the past two decades, dozens of antiangiogenic drugs have been approved for the treatment of a variety of cancers. So far, hundreds of thousands of cancer patients have benefited from antiangiogenesis treatments but limited efficacy and resistance remain outstanding problems. This article will focus on tumor angiogenesis‐related signaling molecules and pathways, development of antiangiogenic agents for the treatment of various tumors, and challenge of antiangiogenic therapy of tumors.

Angiogenic signaling pathways and anti-angiogenic therapy for cancer

“…71,74 In addition to the above three models, tumors can achieve angiogenesis through vessel co-option, vessel mimicry, lymphangiogenesis, and rare stromal-sharing modes. 3,24,75 Vessel cooption, in which tumor cells migrate around pre-existing blood vessels or infiltrate into surrounding tissue space, eventually wrapping the blood vessels and leading them into tumor tissue to supply nutrients for tumor cells (Fig. 2d).…”

“…For example, the combination of bevacizumab, carboplatin, and paclitaxel (or gemcitabine) was approved by FDA for later treatment after bevacizumab monotherapy in platinum-sensitive recurrent epithelial ovarian cancer in 2016. 44,75 Then in 2020, bevacizumab was approved for untreated locally advanced or metastatic RCC in combination with monoclonal antibody atezolizumab, an immune checkpoint inhibitor of PD-L1. 75 Bevacizumab is an anti-angiogenic drug with excellent research and application value, which has great potential for emerging combination therapies to synergy chemotherapeutic drugs and immune checkpoint inhibitors.…”

“…44,75 Then in 2020, bevacizumab was approved for untreated locally advanced or metastatic RCC in combination with monoclonal antibody atezolizumab, an immune checkpoint inhibitor of PD-L1. 75 Bevacizumab is an anti-angiogenic drug with excellent research and application value, which has great potential for emerging combination therapies to synergy chemotherapeutic drugs and immune checkpoint inhibitors. Ramucirumab (Cyramza ® ) is a fully humanized IgG1 antibody with a weight of 147 kDa, which targets the extracellular binding domain of VEGFR-2 to disturb the potent VEGF signal in tumor angiogenesis (Table 1).…”