Enhanced apoptosis with combination C225/radiation treatment serves as the impetus for clinical investigation head and neck cancers

James A. Bonner, Kevin P. Raisch, Hoa Q. Trummell, Francisco Robert, Ruby F. Meredith, Sharon A. Spencer, Donald J. Buchsbaum, Mansoor N. Saleh, Murray A. Stackhouse, Albert F. LoBuglio, Glenn E. Peters, William R. Carroll, Harlan W. Waksal

Research output: Contribution to journalArticlepeer-review

215 Citations (Scopus)

Abstract

Purpose: Epidermal growth factor receptor (EGFr) is overexpressed in a majority of head and neck squamous cell carcinomas, and this overexpression is assodated with a poor prognosis. Therefore, EGFr has become the target of investigations aimed at disabling the receptor to determine whether this process leads to improved tumor kill with conventional treatment. Materials and Methods: C225 is an anti-EGFr monoclonal antibody that inhibits receptor activity by blocking the ligand binding site. A panel of human head and neck scuamous cell carcinoma cell lines was used to study the combination of C225 and radiation. Results: It wa determined that the combination of C225 (5 μg/mL) delivered simultaneously with radiation (3 Gy) resulted in a greater decrement in cellular proliferation than either treatment alone. This reduction in proliferation correlated with reduced EGFr tyrosine phosphorylation and a reduction n phosphorylated signal transducer and activator of transcription-3 (STAT-3) protein (known to protect cells from apoptosis). Also, the decrement in proliferation correlated with increased apoptotic event, thereby indirectly linking C225/radiation-induced regulation of STAT-3 protein to apoptosis. Conclusion: This preclinical work serves as important support for the ongoing clinical investigation of C225 and radiotherapy for patients with head and neck carcinomas. The initial results of these clinical studies have been promising. (C) 2000 by American Society of Clinica Oncology.

Original languageEnglish
Pages (from-to)47s-53s
JournalJournal of Clinical Oncology
Volume18
Issue number21 SUPPL.
Publication statusPublished - 1 Nov 2000
Externally publishedYes

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