Receptor Tyrosine Kinases as Targets for Cancer Therapy Development

摘要

Receptor tyrosine kinases (RTKs) are membrane-spanning proteins that possess a ligand-controlled intracellular kinase activity. They regulate a wide variety of cellular processess as diverse as cell proliferation, apoptosis or cell migration. Consequently, dysregulation of RTKs due to overexpression, mutation or autocrine stimulation has been causally linked to cancer development and progression. The advent of molecular cloning allowed the elucidation of the primary structure of the first RTK, the EGFR. Subsequent research in this field led to tremendous advances in understanding molecular signalling processes governing both physiological and pathophysiological behaviour of cells. These discoveries paved the way for the development of target-specific cancer therapeutics and opened up a new era of molecular targeted approaches in the treatment of human cancer. The approval of monoclonal antibodies such as Herceptin?for the treatment of breast cancer or small molecule inhibitors such as Gleevec?for gastrointestinal stromal tumors underlines both the power and success of this novel strategy.