Anti-VEGF Therapy in Cancer: A Double-Edged Sword

Abstract

Vascular endothelial growth factor (VEGF) is a mitogen that plays a crucial role in angiogenesis and lymphangiogenesis. It is involved in tumor survival through inducing tumor angiogenesis and by increasing chemoresistance through autocrine signaling. Because of its importance in tumor formation and survival, several medications have been developed to inhibit VEGF and reduce blood vessel formation in cancer. Although these medications have proven to be efective for late-stage and metastatic cancers, they have been shown to cause side efects such as hypertension, artery clots, complications in wound healing, and, more rarely, gastrointestinal perforation and istulas. Current research in using anti-VEGF medication as a part of cancer treatments is focusing on elucidating the mechanisms of tumor resistance to VEGF medication, developing predictive biomarkers that assess whether a patient will respond to VEGF therapy and creating novel treatments and techniques that increase the eicacy of antiangiogenic medication. This chapter aims to review the role of VEGF in tumor angiogenesis and metastasis, the structure and function of VEGF and its receptors, and VEGF's role in cancer are discussed. Furthermore, tumor therapies targeting VEGF along with their side efects are presented and, inally, new directions in anti-VEGF therapy are considered along with the challenges.

Case Report: A Case of Pituitary Carcinoma Treated With Sequential Dual Immunotherapy and Vascular Endothelial Growth Factor Inhibition Therapy

“…Adverse effects of VEGFi occur as a result of endothelial dysfunction and include hypertension in up to 32% of patients and proteinuria in 23% of patients, as well as venous and arterial thromboembolic events, cardiotoxicity, impaired wound healing, gastrointestinal perforation, and increased risk of hemorrhagic events (86,87).…”

Neuroimmune Semaphorin 4A in Cancer Angiogenesis and Inflammation: A Promoter or a Suppressor?

“…The main target for angiogenesis-based cancer therapy is VEGF [36]. Currently, there are several small molecule inhibitors and monoclonal antibodies targeting the VEGF-A pathway, with their side-effects analyzed and reported [36].…”

“…The main target for angiogenesis-based cancer therapy is VEGF [36]. Currently, there are several small molecule inhibitors and monoclonal antibodies targeting the VEGF-A pathway, with their side-effects analyzed and reported [36]. Bevacizumab (avastin, recombinant humanized monoclonal Ab to VEGF) is currently used for treatment of metastatic colorectal cancer, non-sqamous non-small cell lung cancer, glioblastoma, metastatic renal cell carcinoma, metastatic or recurrent cervical cancer (in combination with chemotherapy), platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in combination with chemotherapy.…”

“…Indeed, when patients with metastatic colorectal carcinoma were treated with bevacizumab (Avastin, anti-VEGF-A mAb) they showed impaired wound healing and postoperative wound complications [37]. The reported side effects for bevacizumab include sensory neuropathy, hypertension, fatigue, and neutropenia [36]. Neutropenia and hypertension were also reported for ramucirumab use in addition to an increased risk of pneumonia.…”

“…Thus, hypertension is the most known side-effect of VEGF inhibition as the ability of VEGF to decrease a blood pressure is well-documented. Other reported problems include an increased risk of arterial thromboembolic events caused by a disturbed regenerative capacity of endothelial cells [36].…”