[Frontiers in Bioscience 16, 1973-1985, January 1, 2011]

Anti-EGFR monoclonal antibody in cancer treatment: in vitro and in vivo evidence

Anna Elisa Quatrale1, Daniela Petriella1, Letizia Porcelli1, Stefania Tommasi1, Nicola Silvestris2, Giuseppe Colucci2, Angelo Paradiso1, Amalia Azzariti1

1Clinical Experimental Oncology Laboratory, , National Cancer Institute Giovanni Paolo II, Via Hahnemann 10, 70126 Bari, Italy, 2Medical and Experimental Oncology Unit, National Cancer Institute Giovanni Paolo II, Via Hahnemann 10, 70126 Bari, Italy

TABLE OF CONTENTS

1. Abstract
2. Introduction
2.1. MAPK signaling pathway
2.2. phospholipase C signaling pathway
2.3. PI3K/Akt signaling pathway
2.4. JAK / STAT signaling pathway
2.5. SRC/ FAK signaling pathway
2.6. ADCC: antibody-dependent cellular cytotoxicity
3. Cetuximab
3.1. Mechanism of action
3.2. Biological properties
3.2.1. Inhibition of cell cycle progression and induction of apoptosis
3.2.2. Inhibition of angiogenesis, invasion and metastatization
3.2.3. ADCC: antibody-dependent cellular cytotoxicity
4. Matuzumab
4.1. Mechanism of action
4.2. Biological properties
4.2.1. Inhibition of cell cycle progression and induction of apoptosis
4.2.2. Inhibition of angiogenesis, invasion and metastatization
4.2.3. ADCC: antibody-dependent cellular cytotoxicity
5. Nimotuzumab
5.1. Mechanism of action
5.2. Biological properties
5.2.1. Inhibition of cell cycle progression
5.2.2. Inhibition of angiogenesis and induction of apoptosis
5.2.3. ADCC: antibody-dependent cellular cytotoxicity
6. IMC-11F8
6.1. Mechanism of action
6.2. Biological properties
7. Zalutumumab
7.1. Mechanism of action
7.2. Biological properties
8. Panitumimab
8.1. Mechanism of action
8.2. Biological properties
9. Perspectives
10. Acknowledgement
11. References

1. ABSTRACT

The complexity of EGFR signaling network suggests that the receptor could be promising targets for new personalised therapy. In clinical practice two strategies targeting the receptor are available; they utilise monoclonal antibodies, directed towards the extracellular domain of EGFR, and small molecule tyrosine kinase inhibitors, which bind the catalytic kinase domain of the receptor. In this review, we summarise currently known pre-clinical data on the antitumor effects of monoclonal antibodies, which bind to EGFR in its inactive configuration, competing for ligand binding and thereby blocking ligand-induced EGFR tyrosine kinase activation. As a consequence of treatment, key EGFR-dependent intracellular signals in cancer cells are affected. Data explaining the mechanisms of action of anti-EGFR monoclonal antibodies, currently used in clinical setting and under development for the treatment of solid tumors, are revised with the aim to provide an overview of the most important preclinical studies showing the impact of this class of EGFR targeted agents on tumor biology.