Current Pharmaceutical Design - Volume 8, Issue 22, 2002

Activation of signaling pathways following DNA damage induced by topoisomerase (topo) poisons can lead to cell death by apoptosis. NF-κB, a major regulator of the stress response and a negative regulator of apoptosis is often activated following treatment with topoisomerase poisons. Since activation of NF-κB is generally considered to relay an anti-apoptotic signal, inactivation of this signaling molecule is considered to Read More

Receptor tyrosine kinases (RTKs) are cell surface transmembrane proteins responsible for intracellular signal transduction. They are expressed in several cell types and, after activation by growth factor binding, trigger a series of intracellular pathways, leading to a wide variety of cell responses (e.g., differentiation, proliferation, migration and invasion, angiogenesis, survival). Over-expression and / or structural alteration of RTKs Read More

Cancer-homing toxins are a group of man-made cytotoxic molecules targeting cancer cells. In the past decade they have demonstrated potential as cancer therapeutics. These molecules contain a toxin, natural or usually derivatized, connected to a cancerhoming module, such as a monoclonal antibody or growth factor or their derivatives. Various cancer-homing toxins have been designed and tested in cell-lines, ani Read More

Blood-borne drug molecules are transported through as well as around cells in tissue. For small molecule drugs with a molar weight <1000, the wall of the capillary blood vessels in tumors usually is not a barrier. Just after a rise in the drug concentration in the blood, the cells closest to the microvessels are exposed to the highest drug concentrations. Short or long lasting concentration gradients away from the capillary vess Read More

DNA topoisomerases are ubiquitous group of enzymes altering the topology of DNA by concerted breakage and rejoining of the phosphodiester backbone of DNA. The enzymes are classified based on the pattern of DNA cleavage. Type IA enzymes found in all bacteria nick the DNA and attach themselves covalently to the 5' side of the nick during the first transesterification reaction. Most of the information on this group of enzy Read More