[Frontiers in Bioscience 16, 1962-1972, January 1, 2011]

EGFR tyrosine kinases inhibitors in cancer treatment: in vitro and in vivo evidence

Anna Elisa Quatrale1, Letizia Porcelli1, 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
3. Gefitinib
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
4. Erlotinob
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
5. Lapatinib
5.1. Mechanism of action
5.2. Biological properties
5.2.1. Inhibition of cell cycle progression and induction of apoptosis
5.2.2. Inhibition of angiogenesis, invasion and metastatization
6. Perspectives
7. Acknowledgement
8. References

1. ABSTRACT

The increasing understanding of the molecular mechanisms of neoplastic transformation and progression has prompted the search for novel drugs that could interfere with the intracellular targets involved in this process. EGFR is implicated in the development and progression of the majority of the common human epithelial cancer; therefore different agents have been developed to block EGFR activation in cancer cells. This review focuses on EGFR-tyrosine kinase inhibitors in clinical practice that interfere with ATP binding, inhibiting tyrosine kinase activity and subsequently blocking signal transduction from EGFR. We report current knowledge on molecular mechanisms underlying the anticancer activity of EGFR-tyrosine kinase inhibitors in preclinical models, with particular attention to EGFR downstream effectors responsible for treatment efficacy or resistance.