A Splice Form of VEGF, a Potential Anti-Angiogenetic Form of Head and Neck Squamous Cell Cancer Inhibition

Abstract

Angiogenesis, primarily mediated by vascular endothelial growth factor (VEGF), is a fundamental step in the progression and metastasis of head and neck squamous cell carcinoma (HNSCC). Traditional anti-angiogenic therapies that target the VEGF pathway have shown promise but are often associated with significant side effects and variable efficacy due to the complexity of the angiogenic signaling pathway. This review highlights the potential of a specific VEGF splice form, VEGF165b, as an innovative therapeutic target for HNSCC. VEGF165b, unlike standard VEGF, is a natural inhibitor that binds to VEGF receptors without triggering pro-angiogenic signaling. Its distinct molecular structure and behavior suggest ways to modulate angiogenesis. This concept is particularly relevant when studying HNSCC, as introducing VEGF165b's anti-angiogenic properties offers a novel approach to understanding and potentially influencing the disease's dynamics. The review synthesizes experimental evidence suggesting the efficacy of VEGF165b in inhibiting tumor-induced angiogenesis and provides insight into a novel therapeutic strategy that could better manage HNSCC by selectively targeting aberrant vascular growth. This approach not only provides a potential pathway for more targeted and effective treatment options but also opens the door to a new paradigm in anti-angiogenic therapy with the possibility of reduced systemic toxicity. Our investigation is reshaping the future of HNSCC treatment by setting the stage for future research on VEGF splice variants as a tool for personalized medicine.

Keywords: VEGF splice form; VEGF splice variants; VEGF165b; anti-angiogenic therapy; head and neck squamous cell carcinoma; tumor angiogenesis.

Figure 1

VEGF signaling pathways. VEGF binding to VEGFR activates several downstream signaling cascades, including the MAPK pathway (RAF-MEK-MAPK), leading to cell proliferation and survival, and the PI3K pathway (PI3K-AKT), promoting cell growth and survival. These pathways contribute to angiogenesis and are critical in the context of tumor progression.

Figure 2

Focusing on the key issues of target specificity, each element represents a critical factor influencing the efficacy and outcome of cancer treatments.