Cancer research communications · 2026
Window-of-Opportunity Study Utilizing Preoperative Cetuximab in Patients with Head and Neck Cancer.
СтатьяНазвание и аннотация: Перевод в очереди
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Bruce Justine Y, Glazer Tiffany A, Berube Liliana L, Longhurst Colin A, Yu Menggang, Hu Rong, Wieland Aaron M, Harari Paul M, Hartig Gregory K, Iida Mari, Mehta Ranjit K, Lawrence Theodore S, Nyati Mukesh K, Poellmann Michael J, Bu Jiyoon, Nickel Kwangok P, Hong Seungpyo, Wheeler Deric L, Kimple Randall J
Аннотация
PURPOSE: AXL, is a receptor tyrosine kinase implicated in EGFR resistance. The primary objective of this study was to test the hypothesis, generated in preclinical studies, that low AXL correlates with clinical response to cetuximab in patients with head and neck cancer (HNC). The secondary objectives were to further describe the feasibility and safety of preoperative administration of cetuximab.
METHODS: We performed a single-site, single arm, open label, window-of-opportunity study utilizing preoperative cetuximab in 15 patients with HNC. Patients received two doses of cetuximab and underwent resection of their tumor. Biopsies were used to assess AXL expression, change in Ki67 staining, and to establish patient-derived xenografts. scRNA-seq of treated xenograft tissue was used to assess differences between sensitive and resistant tumors.
RESULTS: Fifteen subjects were registered for treatment on the study and fourteen completed treatment with cetuximab prior to surgical resection. No correlation between AXL expression at baseline and change in tumor size in response to cetuximab was seen. Preoperative cetuximab did not delay surgical resection and no unexpected treatment-related adverse events were seen. scRNA-seq identified that cetuximab sensitivity is marked by transcriptional remodeling, while resistance is associated with stable HER signaling and elevated TAM activity.
CONCLUSION: Delivery of preoperative cetuximab is safe, and a short course can be utilized to identify patients with HNC responding to single-agent cetuximab treatment.
METHODS: We performed a single-site, single arm, open label, window-of-opportunity study utilizing preoperative cetuximab in 15 patients with HNC. Patients received two doses of cetuximab and underwent resection of their tumor. Biopsies were used to assess AXL expression, change in Ki67 staining, and to establish patient-derived xenografts. scRNA-seq of treated xenograft tissue was used to assess differences between sensitive and resistant tumors.
RESULTS: Fifteen subjects were registered for treatment on the study and fourteen completed treatment with cetuximab prior to surgical resection. No correlation between AXL expression at baseline and change in tumor size in response to cetuximab was seen. Preoperative cetuximab did not delay surgical resection and no unexpected treatment-related adverse events were seen. scRNA-seq identified that cetuximab sensitivity is marked by transcriptional remodeling, while resistance is associated with stable HER signaling and elevated TAM activity.
CONCLUSION: Delivery of preoperative cetuximab is safe, and a short course can be utilized to identify patients with HNC responding to single-agent cetuximab treatment.