PARENT SESSION
9:00 AM to 11:00 AM
Tuesday, April 23, 2002
Symposium 13
Molecular Inhibition of EGFR: From Lab to Clinic
Room: Tahoe
Chair: Harari, Paul²²Department of Human Oncology, University of Wisconsin, 600 Highland Ave. K4/332, Madison, WI
Speakers: Arteaga, Carlos⁴; Baselga, Jose⁵; Harari, Paul⁶⁴Division of Medical Oncology, Nashville, TN⁵Oncology Service, Barcelona, Spain⁶Dept of Human Oncology, Madison, WI

(S13-1) EGFR inhibition: Rationale and mechanisms.

Arteaga, Carlos^*,1, ¹ Div. Oncology/Vanderbilt University, Nashville, TN

ABSTRACT-
The ability of the EGFR to transform epithelial cells, the overexpression of EGFR and its ligands in several human carcinomas, and the causal association of the receptor network with accelerated tumor progression provided a rationale for targeting this signaling system with tumor-selective strategies. Two of these anti-receptor approaches, both based on the known structure/function of the EGFR, will be discussed. The first strategy has involved the development of humanized monoclonal antibodies against the non-conserved extracellular (EC) domain of the receptor. These antibodies block ligand binding and can induce receptor downregulation. The second approach has been the generation of ATP-mimetics that compete with ATP for binding to the kinase pocket of the receptor and disable the ability of the EGFR to transduce intracellular signals. Early clinical studies already suggest that both of these approaches, either alone or in combination with standard anticancer therapies, including ionizing radiation, alter the natural history of EGFR-expressing cancers with little toxicity to the tumor-bearing host.

KEYWORDS: egf receptors, molecular therapeutics