Biomarkers of Cetuximab Resistance in Patients with Head and Neck Squamous Cell Carcinoma
Overview
Authors
Affiliations
In patients with head and neck squamous cell carcinoma (HNSCC), cetuximab [a monoclonal antibody targeting epidermal growth factor receptor (EGFR)] has been shown to improve overall survival when combined with radiotherapy in the locally advanced setting or with chemotherapy in first-line recurrent and/or metastatic (R/M) setting, respectively. While biomarkers of resistance to cetuximab have been identified in metastatic colorectal cancer, no biomarkers of efficacy have been identified in HNSCC. Here, we aimed to identify biomarkers of cetuximab sensitivity/resistance in HNSCC. HNSCC patients treated with cetuximab at the Curie Institute, for whom complete clinicopathological data and formalin-fixed paraffin-embedded (FFPE) tumor tissue collected before cetuximab treatment were available, were included. Immunohistochemistry analyses of PTEN and EGFR were performed to assess protein expression levels. and mutations were analyzed using high-resolution melting (HRM) and Sanger sequencing. We evaluated the predictive value of these alterations in terms of progression-free survival (PFS). Hot spot activating and mutations were associated with poor PFS among HNSCC patients treated with cetuximab in the first-line R/M setting, but not among HNSCC patients treated with cetuximab in combination with radiotherapy. Loss of PTEN protein expression had a negative predictive value among HNSCC patients treated with cetuximab and radiotherapy. High EGFR expression did not predict cetuximab sensitivity in our patient population. Hot spot activating and mutations predicted cetuximab resistance among HNSCC patients in the first-line R/M setting, whereas loss of PTEN protein expression predicted resistance to cetuximab when combined to radiotherapy.
Dual inhibition of HERs and PD-1 counteract resistance in KRAS-mutant head and neck cancer.
Novoplansky O, Jagadeeshan S, Prasad M, Yegodayev K, Marripati D, Shareb R J Exp Clin Cancer Res. 2024; 43(1):308.
PMID: 39567998 PMC: 11577641. DOI: 10.1186/s13046-024-03227-0.
Zhai P, Tong T, Wang X, Li C, Liu C, Qin X Cell Mol Life Sci. 2024; 81(1):282.
PMID: 38943031 PMC: 11335205. DOI: 10.1007/s00018-024-05324-x.
Understanding PI3K/Akt/mTOR signaling in squamous cell carcinoma: mutated PIK3CA as an example.
Zheng S, He S, Liang Y, Tan Y, Liu Q, Liu T Mol Biomed. 2024; 5(1):13.
PMID: 38616230 PMC: 11016524. DOI: 10.1186/s43556-024-00176-0.
Zahavi D, Erbe R, Zhang Y, Guo T, Malchiodi Z, Maynard R Cancer Biol Ther. 2023; 24(1):2269637.
PMID: 37878417 PMC: 10601508. DOI: 10.1080/15384047.2023.2269637.
A transcriptomics approach to expand therapeutic options and optimize clinical trials in oncology.
Lazar V, Zhang B, Magidi S, Le Tourneau C, Raymond E, Ducreux M Ther Adv Med Oncol. 2023; 15:17588359231156382.
PMID: 37025260 PMC: 10071163. DOI: 10.1177/17588359231156382.