J. Narayanan1*, R. Sridevi1, V. Chitra1, V. Manimaran2, K.
Manikandan3
1Department of
Pharmacology, SRM College of Pharmacy, SRM Institute of Science and Technology,
Kattankulathur, India
2Department of
Pharmaceutics, SRM College of Pharmacy, SRM Institute of Science and Technology,
Kattankulathur, India
3Department of
Pharmaceutical Analysis, SRM College of Pharmacy, SRM Institute of Science and
Technology, Kattankulathur, India
*For Correspondence
narayanj@srmist.edu.in
Abnormalities in the vasculature
of tumors, including undeveloped structure, increased permeability, and a
disorganized microenvironment, are important characteristics of cancer. The
problems are caused by malfunctioning endothelium and mural cellular structures,
in addition to disrupted connections with the extracellular matrix (ECM). Tumor
endothelial cells (TECs) derived from cancer stem cells undergo detachment,
resulting in an elevation of vascular permeability and promoting the
dissemination of the tumor. Pericyte detachment exacerbates these issues by
augmenting mechanical strain and interrupting blood circulation, resulting in a
hypoxic, acidic environment that promotes tumor proliferation and the
production of ascites. Increased levels of Vascular Endothelial Growth Factor
(VEGF) promote angiogenesis, which are abnormal in structure and limit the
efficient delivery of drugs. Tumors can also employ vasculogenic mimicry, which
involves the formation of vascular systems resembling those found in embryos,
in order to get food. VEGF and its related proteins (VEGF-A, VEGF-C, VEGF-D)
play a crucial function in facilitating the development of new blood vessels in
Head and Neck Squamous Cell Carcinoma (HNSCC). Anti-VEGF therapies, comprising
monoclonal antibodies and small molecule inhibitors, offer potential benefits
but face challenges associated with resistance. Inhibiting VEGF receptors with
tyrosine kinase inhibitors (TKIs) can enhance advancement survival without
complications and response rates, particularly when combined with immune
checkpoint inhibitors (ICIs). Currently, there is ongoing research on
FDA-approved tyrosine kinase inhibitors (TKIs) such as sunitinib, sorafenib,
and lenvatinib, in addition to novel medicines like zanzalintinib. Future research
endeavors to augment medicines that target VEGF, incorporate immunotherapy, and
identify biomarkers to boost treatment outcomes for HNSCC.
Keywords
Tumor Angiogenesis, Vascular Endothelial Growth Factor (VEGF) Pathway, Head and Neck Squamous Cell Carcinoma (HNSCC), Tyrosine Kinase Inhibitors (TKIs), Tumor Microenvironment
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