Open Access

REVIEW

Predictive Value of Serum VEGF Levels in Non-Small Cell Lung Cancer: A Review

Eleni Kokkotou^*, Andriani Charpidou, Nikolaos Syrigos

Oncology Unit, Third Department of Medicine, “Sotiria” General Hospital for Chest Diseases, National and Kapodistrian University of Athens, Athens, 11527, Greece

* Corresponding Author: Eleni Kokkotou. Email:

(This article belongs to the Special Issue: Shaping the Future: The Next Evolution of Cancer Immunotherapy)

Oncology Research 2025, 33(10), 2657-2672. https://doi.org/10.32604/or.2025.066228

Received 02 April 2025; Accepted 05 August 2025; Issue published 26 September 2025

Abstract

Vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) serve an essential role in tumor angiogenesis and have emerged as potential therapeutic targets in lung cancer. This review explores the significance of serum VEGF levels as a predictive biomarker in non-small cell lung cancer (NSCLC). The VEGF family, consisting of VEGFA, VEGFB, VEGFC, VEGFD, and placenta growth factor (PlGF), engages with specific receptors, including tyrosine kinase receptors (VEGFR-1, VEGFR-2, and VEGFR-3) and neuropilin receptors (NRP-1 and NRP-2), to promote angiogenesis and lymphangiogenesis. VEGF-A, the primary component of the VEGF family, binds to VEGFR-2 to stimulate endothelial cell proliferation and migration, while VEGF-B, VEGF-C, and VEGF-D interact with VEGFR-1 and VEGFR-3 to regulate tumor angiogenesis, lymphangiogenesis, and metastasis. The VEGF/VEGFR signaling pathway activates various downstream effectors, including phospholipase Cγ1, mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), which are essential for maintaining vascular homeostasis and promoting angiogenesis. In NSCLC, elevated serum VEGF levels have been observed, and the VEGF/VEGFR axis is frequently impaired, leading to irregular blood vessel formation and metastatic spread. Despite the development of anti-VEGF therapies, their impact on lung cancer outcomes has been limited. Further research is needed to optimize the effectiveness of these treatments and elucidate the potential of serum VEGF as a predictive biomarker in NSCLC.

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