Targeting <scp>VEGF</scp> with bevacizumab inhibits malignant effusion formation of primary human herpesvirus 8‐unrelated effusion large B‐cell lymphoma in vivo

Ogasawara, Fumiya; Higuchi, Tomonori; Nishimori, Tomohiro; Hashida, Yumiko; Kojima, Kensuke; Daibata, Masanori

doi:10.1111/jcmm.17570

Cited by 2 publications

(1 citation statement)

References 38 publications

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“…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 . Notably, RBD of VEGF‐A is the main target of this antibody.…”

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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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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Targeting VEGF with bevacizumab inhibits malignant effusion formation of primary human herpesvirus 8‐unrelated effusion large B‐cell lymphoma in vivo

Ogasawara

Higuchi

Nishimori

et al. 2022

J Cellular Molecular Medi

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Large B-cell lymphomas that grow exclusively in body cavity effusions without identifiable tumour masses are universally associated with human herpesvirus 8 (HHV8), also called Kaposi sarcomaassociated herpesvirus, and this lymphoma entity is defined as primary effusion lymphoma (PEL) according to the 2017 World Health Organization classification. 1 PEL often appears with Epstein-Barr virus (EBV), especially in the setting of human immunodeficiency virus (HIV) infection. 1 PEL has a characteristic phenotype in that it lacks pan-B-cell markers such as CD19 and CD20 but expresses plasma cell markers such as CD138. [1][2][3] Primary HHV8-unrelated effusion lymphoma, hereinafter referred to as HHV8-unrelated effusion large B-cell lymphoma

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Targeting VEGF with bevacizumab inhibits malignant effusion formation of primary human herpesvirus 8‐unrelated effusion large B‐cell lymphoma in vivo

Cited by 2 publications

References 38 publications

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

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

Targeting VEGF with bevacizumab inhibits malignant effusion formation of primary human herpesvirus 8‐unrelated effusion large B‐cell lymphoma in vivo

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