Principles of receptor-based inhibition of erbB family receptor kinases: prospects for new therapies for human cancers.
The erbB family of receptor tyrosine kinases is composed of growth factor receptors that are overexpressed or mutated in a large variety of human cancers. The study of erbB-mediated signal transduction will lead to an understanding of the role played by this family of receptors in normal and transformed cells. In this article, we discuss the contemporary understanding of the structure and function of these receptors and how these features might be exploited in receptor-based strategies of growth inhibition. The first part of our study details the structure of erbB receptors as it relates to the process of transformation of cells and the malignant phenotype in humans. In the second part, we discuss two rational approaches to therapy for cancers in which erbB receptors are overexpressed or mutated: first, the potential for antireceptor immunity and the evolution of small molecules for receptor-based immunotherapy; second, a strategy of ectodomain association that leads to the formation of defective kinase assemblies. These studies provide a basis for the application of receptor-based strategies of growth inhibition in erbB-expressing human cancers.
O'Rourke
D M
DM
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Zhang
X
X
Greene
M I
MI
D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D015398:Signal Transduction
D004791:Enzyme Inhibitors; D066246:ErbB Receptors