EGFR isoforms might be responsible for the diminished treatment outcome of EGFR inhibitors

Rajdeep Chakraborty; Pallavi Khodlan; Arthur Chien; Chao Shen; Thiri Winn; Matthew Fitzhenry; Ardeshir Amirkhani; Fei Liu

doi:10.1177/0976500X251321892

EGFR isoforms might be responsible for the diminished treatment outcome of EGFR inhibitors

Rajdeep Chakraborty^*, Pallavi Khodlan, Arthur Chien, Chao Shen, Thiri Winn, Matthew Fitzhenry, Ardeshir Amirkhani, Fei Liu

^*Corresponding author for this work

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Abstract

Epidermal growth factor receptor (EGFR) plays an active role during the progression of oral squamous cell carcinoma (OSCC). OSCC is the most common head and neck cancer. Cetuximab, which is an inhibitor of EGFR, was approved by the Food and Drug Administration (FDA) in 2006 for the treatment of head and neck cancer. After initial clinical success, Cetuximab proved to be ineffective in the management of aggressive or metastatic oral cancer lesions. We hypothesize that EGFR has multiple isoforms that lead to the failure of Cetuximab. A future study of EGFR isoforms and protein-interacting partners will address the issue.

Original language	English
Pages (from-to)	145-147
Number of pages	3
Journal	Journal of Pharmacology and Pharmacotherapeutics
Volume	17
Issue number	1
Early online date	13 Mar 2025
DOIs	https://doi.org/10.1177/0976500X251321892
Publication status	Published - Mar 2026

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Copyright the Author(s) 2025. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

EGFR
OSCC
Isoform
Oral cancer
epidermal growth factor receptor
Anti-tumor reactivity
Cetuximab
oral cancer

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10.1177/0976500X251321892Licence: CC BY-NC

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Cite this

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title = "EGFR isoforms might be responsible for the diminished treatment outcome of EGFR inhibitors",

abstract = "Epidermal growth factor receptor (EGFR) plays an active role during the progression of oral squamous cell carcinoma (OSCC). OSCC is the most common head and neck cancer. Cetuximab, which is an inhibitor of EGFR, was approved by the Food and Drug Administration (FDA) in 2006 for the treatment of head and neck cancer. After initial clinical success, Cetuximab proved to be ineffective in the management of aggressive or metastatic oral cancer lesions. We hypothesize that EGFR has multiple isoforms that lead to the failure of Cetuximab. A future study of EGFR isoforms and protein-interacting partners will address the issue. ",

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T1 - EGFR isoforms might be responsible for the diminished treatment outcome of EGFR inhibitors

AU - Chakraborty, Rajdeep

AU - Khodlan, Pallavi

AU - Chien, Arthur

AU - Shen, Chao

AU - Winn, Thiri

AU - Fitzhenry, Matthew

AU - Amirkhani, Ardeshir

AU - Liu, Fei

N1 - Copyright the Author(s) 2025. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2026/3

Y1 - 2026/3

N2 - Epidermal growth factor receptor (EGFR) plays an active role during the progression of oral squamous cell carcinoma (OSCC). OSCC is the most common head and neck cancer. Cetuximab, which is an inhibitor of EGFR, was approved by the Food and Drug Administration (FDA) in 2006 for the treatment of head and neck cancer. After initial clinical success, Cetuximab proved to be ineffective in the management of aggressive or metastatic oral cancer lesions. We hypothesize that EGFR has multiple isoforms that lead to the failure of Cetuximab. A future study of EGFR isoforms and protein-interacting partners will address the issue.

AB - Epidermal growth factor receptor (EGFR) plays an active role during the progression of oral squamous cell carcinoma (OSCC). OSCC is the most common head and neck cancer. Cetuximab, which is an inhibitor of EGFR, was approved by the Food and Drug Administration (FDA) in 2006 for the treatment of head and neck cancer. After initial clinical success, Cetuximab proved to be ineffective in the management of aggressive or metastatic oral cancer lesions. We hypothesize that EGFR has multiple isoforms that lead to the failure of Cetuximab. A future study of EGFR isoforms and protein-interacting partners will address the issue.

KW - EGFR

KW - OSCC

KW - Isoform

KW - Oral cancer

KW - epidermal growth factor receptor

KW - Anti-tumor reactivity

KW - Cetuximab

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DO - 10.1177/0976500X251321892

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JO - Journal of Pharmacology and Pharmacotherapeutics

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IS - 1

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EGFR isoforms might be responsible for the diminished treatment outcome of EGFR inhibitors

Abstract

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