Receptor tyrosine kinases and anticancer therapy

Abstract

Receptor and non-receptor protein tyrosine kinases (PTKs) are essential enzymes in cellular signaling processes and signal transduction pathways that regulate cell growth, differentiation, migration and metabolism by catalyzing protein phosphorylation and dephosphorylation. In recent years, different tyrosine kinase receptors were identified as regulators of tumor or tumor vessel growth. Their inhibition by specific tyrosine kinase inhibitors and antibodies targeting growth factors and their receptors were recently shown to constitute a new modality for treating cancers. The pathognomonic role of the inhibited tyrosine kinase defines the way of action, whereas the amount of expression in tumor tissue is thought to define the indication for the tumor entity. Various compounds targeting PTKs are under clinical investigation in phase I-III trials or are already approved. This review describes new drugs targeting BCR-Abl, c-kit, EGFR (epidermal growth factor receptor), tumor angiogenesis via VEGF (vascular endothelial growth factor), HER2/neu and "multitarget" tyrosine kinase inhibitors.