From Tyrphostins to Iressa and Gleevec: Signal Transduction Therapy from Concept to the Patient Bed

Protein tyrosine kinases (PTK’s) is a unique family of protein kinases, whose members are all involved in intercellular and intracellular communications. They were the first family of proteins whose aberrant activities have been directly related to human malignancies. Therefore, they became the first set of novel therapeutic targets for the development of “signal transduction therapy”. The goal of this therapy is to manipulate aberrant signal transduction pathways in order to bring the demise of the cancer cell Since protein tyrosine kinases (PTKs) play a major role in driving cancer cells and lending them their anti-apoptotic robustness they were identified as targets for drug development. Tyrosine phosphorylation inhibitors (tyrphostins) were developed with the aim of blocking the enhanced signaling of PTK’s in cancer cells, and thus induce their apoptotic death. The principles of the approach, its successes and failures are discussed.