TY - JOUR
T1 - A narrative review of the role of Eph receptors in head and neck squamous cell carcinoma
AU - Al-Jamaei, Aisha A. H.
AU - Subramanyam, Ramadugula V.
AU - Helder, Marco N.
AU - Forouzanfar, Tymour
AU - van der Meij, Erik H.
AU - Al-Jamei, Sayida
AU - de Visscher, Jan G. A. M.
N1 - Publisher Copyright: © 2023 The Authors. Oral Diseases published by Wiley Periodicals LLC.
PY - 2023
Y1 - 2023
N2 - Tyrosine kinase receptors (TKR) coordinate a variety of pathological processes in head and neck squamous cell carcinoma (HNSCC), and eventually play a role in patient outcomes. In this review, the role of Eph receptors in HNSCC progression and the possibility of targeting these receptors are illustrated. All relevant studies were identified through a comprehensive search of four electronic databases, including PubMed, Scopus, web of science, and Embase till August 2022. EphA2 and EphB4, along with ephrin-B2, were the most extensively studied proteins in this family. However, overexpression of EphB4 and its ligand ephrin-B2 were the only proteins that consistently showed association with a poor outcome, indicating that these proteins might serve as valuable prognostic markers in HNSCC. High expression of EphA3 and EphB4 was found to play a crucial role in radioresistance of HNSCC. EphB4 loss, in particular, was observed to induce an immunosuppression phenotypic HNSCC. Currently, ongoing clinical trials are investigating the benefits of EphB4-ephrin-B2 blockade in combination with standard of care treatment in HNSCC. Further efforts are needed to explore the biological role and behavioral complexity of this family of TKR in HNSCC with great attention to avoid heterogeneity of HNSCC subsites.
AB - Tyrosine kinase receptors (TKR) coordinate a variety of pathological processes in head and neck squamous cell carcinoma (HNSCC), and eventually play a role in patient outcomes. In this review, the role of Eph receptors in HNSCC progression and the possibility of targeting these receptors are illustrated. All relevant studies were identified through a comprehensive search of four electronic databases, including PubMed, Scopus, web of science, and Embase till August 2022. EphA2 and EphB4, along with ephrin-B2, were the most extensively studied proteins in this family. However, overexpression of EphB4 and its ligand ephrin-B2 were the only proteins that consistently showed association with a poor outcome, indicating that these proteins might serve as valuable prognostic markers in HNSCC. High expression of EphA3 and EphB4 was found to play a crucial role in radioresistance of HNSCC. EphB4 loss, in particular, was observed to induce an immunosuppression phenotypic HNSCC. Currently, ongoing clinical trials are investigating the benefits of EphB4-ephrin-B2 blockade in combination with standard of care treatment in HNSCC. Further efforts are needed to explore the biological role and behavioral complexity of this family of TKR in HNSCC with great attention to avoid heterogeneity of HNSCC subsites.
KW - Eph receptors
KW - expression
KW - head and neck cancer
KW - head and neck squamous cell carcinoma
KW - metastasis
KW - targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=85161612324&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/odi.14625
DO - https://doi.org/10.1111/odi.14625
M3 - Review article
C2 - 37279081
SN - 1354-523X
JO - Oral diseases
JF - Oral diseases
ER -