The Use of Epidermal Growth Factor Receptor Monoclonal Antibodies in Squamous Cell Carcinoma of the Head and Neck

Abstract

Targeting of the EGF receptor (EGFR) has become a standard of care in several tumor types. In squamous cell carcinoma of the head and neck, monoclonal antibodies directed against EGFR have become a regular component of therapy for curative as well as palliative treatment strategies. These agents have anti-tumor efficacy as a single modality and have demonstrated synergistic tumor killing when combined with radiation and/or chemotherapy. While cetuximab has been the primary anti-EGFR monoclonal antibody used in the US, variant anti-EGFR monoclonal antibodies have been used in several clinical studies and shown benefit with improved toxicity profiles. Next generation anti-EGFR monoclonal antibodies may demonstrate multi-target epitope recognition, enhanced immune cell stimulation, or conjugation with radioisotopes in order to improve clinical outcomes. Identification of the specific patient subset that would optimally benefit from anti-EGFR monoclonal antibodies remains an elusive goal.

Magnetic Nanoparticles as Mediators of Ligand-Free Activation of EGFR Signaling

“…Monoclonal antibodies that block ligand binding inhibit EGFR signaling and some cause down regulation of the receptor [26], [27], [28], suggesting that ligand binding is indeed required for EGFR activation. Some of these antibodies have been humanized and used to treat cancers expressing high levels of EGFR [29], [30], [31]. Certain mutations of EGFR cause a constitutive ligand independent activation of the receptor and such forms often arise under conditions favoring cellular transformation [32], [33].…”

Paclitaxel in combination with cetuximab exerts antitumor effect by suppressing NF-κB activity in human oral squamous cell carcinoma cell lines

“…Most of the available reports on HNSCC demonstrated the effect of cetuximab in combination with cisplatin/platinumbased drugs or radiotherapy (7,13,14). However, cetuximab with paclitaxel combination therapy has been proven to be effective in HNSCC including several other cancers (15)(16)(17)(18)(19).…”

“…Almost 60% of HNSCC patients are diagnosed with locally advanced disease at presentation (6). Therefore, it is important to establish more promising therapeutic strategies.Cetuximab (Erbitux ® ; formerly IMC-C225) is a chimeric (mouse/human) IgG1 monoclonal antibody that targets the extracellular ligand-binding domain of EGFR with high affinity and inhibits tumor growth, invasion, angiogenesis and metastasis (7,8). Cetuximab causes G1 phase cell cycle arrest by decreasing cyclin-dependent kinase 2 (CDK2) and increasing p27…”

“…Paclitaxel (PTX) is a diterpenoid isolated from the bark of the Pacific yew, Taxus brevifolia (10). PTX induces mitotic arrest and cell death by binding to microtubules, promoting microtubule assembly, and stabilizing tubulin polymers against depolymerization affecting cells in the G2/M-phase (11,12).Most of the available reports on HNSCC demonstrated the effect of cetuximab in combination with cisplatin/platinumbased drugs or radiotherapy (7,13,14). However, cetuximab with paclitaxel combination therapy has been proven to be effective in HNSCC including several other cancers (15)(16)(17)(18)(19).…”

NADPH Oxidase Biology and the Regulation of Tyrosine Kinase Receptor Signaling and Cancer Drug Cytotoxicity

“…In general, EGFR mutation is correlated with a poor clinical prognosis. The molecular analysis of EGFR gene mutations is used as a guideline protocol to determine the prescription of EGF signaling tyrosine kinase inhibitors, such as erlotinib, and monoclonal antibodies (mAbs) against EGFR, such as cetuximab (chimeric mAb) and panitumumab (humanised mAb), as single agents or associated with standard chemotherapy and/or radiotherapy protocols [72,73]. …”