The role of VEGF in cancer-induced angiogenesis and research progress of drugs targeting VEGF

Ghalehbandi, Seyedehdelaram; Yuzugulen, Jale; Pranjol, Zahidul Islam; Pourgholami, Mohammad H.

doi:10.1016/j.ejphar.2023.175586

Cited by 62 publications

(37 citation statements)

References 256 publications

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“…Angiogenesis is essential for cancer development and growth, because it requires blood vessels to supply nutrients and oxygen 25 . The production of VEGF and other growth factors by the tumor results in the “angiogenic switch,” where new vasculature is formed in and around the tumor, allowing it to grow exponentially 26 . In this study, we found the Xiaotan Sanjie Fang was able to reduce the expression of VEGF.…”

Section: Discussionmentioning

confidence: 66%

“…25 The production of VEGF and other growth factors by the tumor results in the "angiogenic switch," where new vasculature is formed in and around the tumor, allowing it to grow exponentially. 26 In this study, we found the Xiaotan Sanjie Fang was able to reduce the expression of VEGF. Suggesting the treatment of Xiaotan Sanjie Fang was capable of suppressing angiogenesis in colorectal cancer precursor lesions when compared to model group.…”

Section: Xiaotan Sanjie Fang Inhibits Apoptosismentioning

confidence: 64%

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Xiaotan Sanjie Fang prevents colonic inflammation‐related tumorigenesis by inhibiting COX‐2/VEGF expression cancer

Ye,

Du,

Chen

et al. 2023

Precision Medical Sciences

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Colitis‐associated bowel cancer (CAC) is one of the most common malignancies associated with inflammation. The aim of this study was to observe a new herbal formula “Xiaotan Sanjie Fang” (XTSJF) derived from the addition and subtraction theory of traditional medicine as an alternative to CAC treatment by “Daotan Decoction” and “Xiaojianzhong Decoction”, which are famous traditional Chinese medicine prescriptions for the treatment of inflammatory diseases of the digestive tract. We constructed a DMH/DSS inflammation‐associated colorectal cancer rat model and treated CAC rats with sulfasalazine and different doses of XTSJF. The results showed that the body weight of rats treated with different doses of XTSJF increased, which was still lower than that of normal rats; AFC decreased significantly compared with the model group and the positive control group, and the final dose was superior to the low dose; histological observation revealed that it could maintain the normal structure of colon tissue, while it could inhibit the secretion of VEGF, COX2, and AQP1 and the expression of pro‐inflammatory cytokines IL‐6, IL‐1β, and TNF‐α, promote the expression of caspase‐3 and BAX and inhibit the expression of Bcl‐2. Taken together, these data suggest that XTSJF can inhibit COX‐2/VEGF expression to prevent the development of inflammation‐associated colorectal cancer.

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Section: Discussionmentioning

confidence: 66%

Section: Xiaotan Sanjie Fang Inhibits Apoptosismentioning

confidence: 64%

Xiaotan Sanjie Fang prevents colonic inflammation‐related tumorigenesis by inhibiting COX‐2/VEGF expression cancer

Ye,

Du,

Chen

et al. 2023

Precision Medical Sciences

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“…The FDA has approved VEGFR inhibitors like sorafenib, sunitinib, pazopanib, regorafenib, cabozantinib, axitinib, vandetanib, lenvatinib and mAb like ramucirumab for cancer treatment 31–33 . Similarly, there are two FDA approved VEGF inhibitors, that is, bevacizumab and aflibercept, used to inhibit tumorigenesis by blocking angiogenesis 34 . Bevacizumab is a humanized mAb, that is used to target the VEGF RBD to inhibit circulating VEGF interaction with VEGFR 35 .…”

Section: Discussionmentioning

confidence: 99%

Nonsynonymous mutations in VEGF receptor binding domain alter the efficacy of bevacizumab treatment

Ahamed,

Samanta,

Alam

et al. 2024

J of Cellular Biochemistry

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Vascular endothelial growth factor (VEGF) mediated angiogenesis is crucial for tumor progression. Isoforms of VEGF bind to different VEGF receptors (VEGFRs) to initiate angiogenesis specific cellular signaling. Inhibitors that target both the receptors and ligands are in clinical use to impede angiogenesis. Bevacizumab, a monoclonal antibody (mAb) approved by the Food and Drug Administration (FDA), binds in the VEGF receptor binding domain (RBD) of all soluble isoforms of VEGF and inhibits the VEGF‐VEGFR interaction. Bevacizumab is also used in combination with other chemotherapeutic agents for a better therapeutic outcome. Understanding the intricate polymorphic character of VEGFA gene and the influence of missense or nonsynonymous mutations in the form of nonsynonymous polymorphisms (nsSNPs) on RBD of VEGF may aid in increasing the efficacy of this drug. This study has identified 18 potential nsSNPs in VEGFA gene that affect the VEGF RBD structure and alter its binding pattern to bevacizumab. The mutated RBDs, modeled using trRosetta, in addition to the changed pattern of secondary structure, post translational modification and stability compared to the wild type, have shown contrasting binding affinity and molecular interaction pattern with bevacizumab. Molecular docking analysis by ClusPro and visualization using PyMol and PDBsum tools have detected 17 nsSNPs with decreased binding affinity to bevacizumab and therefore may impact the treatment efficacy. Whereas VEGF RBD expressed due to rs1267535717 (R229H) nsSNP of VEGFA has increased affinity to the mAb. This study suggests that genetic characterization of VEGFA before bevacizumab mediated cancer treatment is essential in predicting the appropriate efficacy of the drug, as the treatment efficiency may vary at individual level.

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“…Therapies targeting VEGF or the VEGF receptor (VEGFR) can be categorized into two types: (i) Drugs such as neutralizing monoclonal antibodies or soluble receptor decoys, that bind to VEGF, disrupting its interaction with VEGFR. (ii) Inhibiting VEGFR downstream signal transduction by either monoclonal antibodies against VEGFR or receptor tyrosine kinase inhibitors (TKI) 28 . Bevacizumab, which works by neutralizing VEGFA, was approved for treating patients with late‐stage colorectal cancer in 2004 29 .…”

Section: Anti‐angiogenic and Immune Therapies In Cancer Managementmentioning

confidence: 99%

Anti‐angiogenic therapy enhances cancer immunotherapy: Mechanism and clinical application

Li,

Fang

2024

Interdisciplinary Medicine

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Immunotherapy, specifically immune checkpoint inhibitors, is revolutionizing cancer treatment, achieving durable control of previously incurable or advanced tumors. However, only a certain group of patients exhibit effective responses to immunotherapy. Anti‐angiogenic therapy aims to block blood vessel growth in tumors by depriving them of essential nutrients and effectively impeding their growth. Emerging evidence shows that tumor vessels exhibit structural and functional abnormalities, resulting in an immunosuppressive microenvironment and poor response to immunotherapy. Both preclinical and clinical studies have used anti‐angiogenic agents to enhance the effectiveness of immunotherapy against cancer. In this review, we concentrate on the synergistic effect of anti‐angiogenic and immune therapies in cancer management, dissect the direct effects and underlying mechanisms of tumor vessels on recruiting and activating immune cells, and discuss the potential of anti‐angiogenic agents to improve the effectiveness of immunotherapy. Lastly, we outline challenges and opportunities for the anti‐angiogenic strategy to enhance immunotherapy. Considering the increasing approval of the combination of anti‐angiogenic and immune therapies in treating cancers, this comprehensive review would be timely and important.

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The role of VEGF in cancer-induced angiogenesis and research progress of drugs targeting VEGF

Cited by 62 publications

References 256 publications

Xiaotan Sanjie Fang prevents colonic inflammation‐related tumorigenesis by inhibiting COX‐2/VEGF expression cancer

Xiaotan Sanjie Fang prevents colonic inflammation‐related tumorigenesis by inhibiting COX‐2/VEGF expression cancer

Nonsynonymous mutations in VEGF receptor binding domain alter the efficacy of bevacizumab treatment

Anti‐angiogenic therapy enhances cancer immunotherapy: Mechanism and clinical application

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