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Growth Factor Receptor Tyrosine Kinases: Cell Adhesion Kinase Family Suggests a Novel Signaling Mechanism in Cancer

Abstract Future advances in oncology will increasingly rely on an understanding of the molecular biology of tumorigenesis. Recent laboratory work has elucidated many molecular events contributing to tumor formation. In particular, the signaling pathways for growth factors have been implicated in the genesis and maintenance of several human tumors (1). Growth factor autocrine and paracrine stimulatory loops promote tumor proliferation and angiogenesis. A family of structurally related growth factor receptors, the receptor tyrosine kinases (RTKs), are particularly relevant to cancer biology. This large family includes the receptors for epidermal growth factor, the platelet-derived growth factor, the fibroblast growth factor, the insulin-like growth factor, the neurotrophins related to nerve growth factor, the vascular endothelial growth factor, the ephrins, and several receptors for which no growth factor ligand has been identified. Several of these receptor molecules and their growth factor ligands are preferentially expressed in the embryo and are thought to play a central role in regulating the determination of cell fate during development. Moreover, the overexpression or mutation of genes encoding these receptors can be oncogenic. Researchers believe that some receptors in this family, those that have been shown to be overexpressed or mutated in human tumors, contribute to cancer formation.