Development of Protein Kinase C and Cyclin-Dependent Kinase Inhibitors As Potentiators of Cytotoxic Drug Action in Leukemia

摘要: During the last decade, approach to cancer chemotherapy has been revolutionized by two major advances: an accelerated understanding of cell-death process (apoptosis) (1) and progress in development molecularly targeted agents directed against specific oncogenes enzymes responsible for neoplastic transformation, e.g., STI571 case Bcr/Abl+ malignancies (2). Such efforts have served focus attention on general classes agents: inhibitors (a) cell-cycle regulation (b) cytoprotective signal transduction pathways. The rationale developing is based abundant evidence that cells are defective regulation, i.e., loss G1 checkpoint (3). In addition, it now recognized a variety cells, particularly those hematopoietic origin, exhibit increased activity certain pro-survival signaling pathways, Ras/Raf/MEK/MAP kinase cascade (4). Thus, interference with progression and/or pathways represents logical alternative (or adjunct) use cytotoxic agents, which kill through more mechanisms.