Targeting Oncogenes in Hematopoietic Malignancies

摘要: The development of the first successful treatments for leukemia owed much more to empiric observation than rational drug design in an era when biology was poorly understood. While cytotoxic chemotherapeutic drugs have played, and continue play, essential role cancer management, their relative lack specificity frequency resistance been a limit this approach. This has prompted search targeted therapies, with goal maximizing responses while minimizing toxicity. requires identification good targets, it is only relatively recently that we had necessary tools undertake process. To be considered target, oncogene product should clearly responsible molecular pathogenesis disease. It protein mutated or aberrantly expressed event being critical malignant Advances fields cytogenetics, genetics, biochemistry over past half century greatly advanced our understanding helped identify candidate targets. We now know oncogenic activation can result from several different mechanisms, including chromosomal translocations, activating mutations, loss function deletions. chapter will show how application knowledge aided molecularly based treatment approaches, particular Bcr-Abl tyrosine kinase inhibitor STI571.