pki-166 and Colorectal-Neoplasms

The epidermal growth factor receptor (EGFR) is the prototypical member of the erbB receptor family. The EGFR axis is activated by a variety of ligands that are crucial in the formation and propagation of many tumors, including colorectal cancer, through their effects on cell signaling pathways, cellular proliferation, control of apoptosis, and angiogenesis. The importance of the EGFR axis in tumorigenesis and tumor progression makes it an attractive target for the development of anticancer therapies. A variety of targeting strategies to exploit the role of EGFR in tumors have been employed. The most highly developed of these anti-EGFR approaches are the monoclonal antibodies and the tyrosine kinase inhibitors (TKIs). Clinical evaluations of these compounds have yielded some promising results. The role of the EGFR axis in colorectal cancer formation and progression is reviewed and the clinical development of these anticancer EGFR-targeted drugs is reviewed and updated.

Topics: Aminoquinolines; Aniline Compounds; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Cell Transformation, Neoplastic; Cetuximab; Colorectal Neoplasms; Disease Progression; ErbB Receptors; Erlotinib Hydrochloride; Gefitinib; Humans; Lapatinib; Organic Chemicals; Panitumumab; Prognosis; Pyrimidines; Pyrroles; Quinazolines; Signal Transduction

The epidermal growth factor receptor (EGFR) plays an important role in the carcinogenesis of many human malignancies and is therefore an attractive target against which anticancer therapy may be effective. At present, there are two ways in which this may be achieved clinically: antibodies against EGFR and inhibitors of the EGFR tyrosine kinase. This review describes presently approved agents cetuximab (monoclonal EGFR antibody), gefitinib and erlotinib (EGFR tyrosine kinase inhibitors) in detail. Efficacy data for these agents in various human malignancies is presented. Various other agents that are in the early stages of development at present have also been mentioned.

Topics: Administration, Oral; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Cetuximab; Colorectal Neoplasms; Drug Delivery Systems; Drug Evaluation, Preclinical; ErbB Receptors; Erlotinib Hydrochloride; Gefitinib; Humans; Lung Neoplasms; Panitumumab; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Quinazolines; Randomized Controlled Trials as Topic