Current Drug Targets - Volume 5, Issue 4, 2004

This issue of CURRENT DRUG TARGETS is focused on cancer therapy, one of the most challenging problems for humanity. Indeed, this problem represents the nexus of life science with many other disciplines. Outburst of modern biology uncovers the fundamental mechanisms of single cell behavior (e.g., gene expression regulation, macromolecular biosynthesis and transport, cell cycle progression, division, death) which, in Read More

Some types of cancer respond far less favorably to treatment than do others. A quantitative estimate of this intuition can be obtained from the SEER (Surveillance, Epidemiology and End-Results) Cancer Statistics Review. Of particular interest, from a drug resistance perspective, are the five-year survival data for patients presenting with tumors that were diagnosed as “distant”. A good correlation can be found between those Read More

Since late 1950s the main strategies to treat cancer, besides surgery, have been radiotherapy or chemotherapy. These approaches work primarily by damaging proliferating cells at the level of DNA replication or cell division, and inducing apoptotic cell suicide as a secondary response to the damage. In recent years, efforts to improve cancer therapy have focused on the development of more selective, biological mechanism Read More

Poly(ADP-ribose) polymerization is a unique post-translation protein modification that utilizes an ADP-ribose moiety from NAD+ to form long and branched polymers attached via glutamic acid residues to nuclear acceptor proteins. The corresponding enzyme, poly(ADPribose) polymerase (PARP-1), is a zinc finger-containing protein, which allows PARP-1 binding to either double- or single-strand DNA breaks. The catalytic acti Read More

Proteins containing a caspase-associated recruitment domain (CARD) have been established as key regulators of cell death and, more recently, cytokine production. During the last several years, the number of proteins identified within this family has grown immensely and many aspects of their function point to their potential utility as novel drug targets in the treatment of cancer. Several CARD family proteins are critical co Read More

Treatment with anti-cancer agents in most cases ultimately results in apoptotic cell death of the target tumor cells. Unfortunately, tumor cells can develop multidrug resistance, e.g., by a reduced propensity to engage in apoptosis by which they become insensitive to multiple chemotherapeutics. Ceramide, the central molecule in cellular sphingolipid metabolism, has been recognized as an important mediator Read More

The efficacy of cancer therapy is compromised by the fact that there are currently no good ways to predict which patients will benefit from treatment. This long standing goal is closer to becoming a reality as more is learned about the molecules that affect the activities of various therapeutic agents. The fluoropyrimidine antimetabolites drugs have been in clinical use for over 4 decades and the cellular proteins im Read More

This review presents molecular targeting approaches in anticancer drug delivery systems (DDS) and identifies new developments in these systems. Targeting approaches include passive targeting (enhanced permeability and retention effect), targeting specific tumor conditions, topical delivery and active targeting, namely, targeting organs, cells, intracellular organelles and molecules, sandwich targeting, promoter targeting, ind Read More