Current Pharmaceutical Design - Volume 6, Issue 4, 2000

There are currently over 80 agents officially approved for the treatment of cancer world-wide. However, the most common epithelial cancers, which cause greater than 75percenr of cancer deaths, remain incurable. Most drugs have been developed empirically by testing large numbers of chemicals on rapidly growing transplantable rodent tumors, and more recently, human tumor xenografts. This approach has identified p Read More

A number of potential molecular targets for novel anticancer drug discovery have been identified in cell cycle control mechanisms. Prominent among these are the regulatory proteins, cyclins and their effector counterparts the cyclin dependent kinases (CDKs). Aberrant expression of these proteins, particularly cyclins involved in the G1 phase of the cell cycle, namely the D and E cyclins, has been associated with a variety of Read More

The MDM2 oncogene was first cloned as an amplified gene on a murine double-minute chromosome in the 3T3DM cell line, a spontaneously transformed derivative of BALB/c 3T3 cells. The MDM2 oncogene has now been shown to be amplified or overexpressed in many human cancers. It also has been suggested that MDM2 levels are associated with poor prognosis of several human cancers. The most exciting finding is th Read More

Angiogenesis is the process by which new blood vessels are formed from preexisting microvasculature. To ensure an adequate blood supply, tumor cells release angiogenic factors that are capable of promoting nearby blood vessels to extend vascular branches to the tumor. In addition, larger tumors have been shown to release angiogeneic inhibitory factors that prevent blood vessels from sending branches to smaller, more di Read More

G-rich DNA sequences can adopt unusual four-stranded DNA structures, called G-quadruplex DNA. Variations in the molecularity, topology, strand orientation, and glycosidic conformation of the G-quadruplex DNA provide a diverse array of structures. Although G-quadruplex structures have only been observed in vitro, strong indirect evidence for their existence in vivo comes from the characterization of G-quadruplex DNA bi Read More

The phrase molecular target-based drug discovery usually implies an in vitro biochemical assay or battery of assays. One portion of the U.S. National Cancer Institutes drug discovery program, to the contrary, examines molecular targets for cancer therapy in a cell-based format. That approach has a number of sig-nificant limitations, but it has produced databases of significant utility on the activities and structures of te Read More

Tumorigenesis is accompanied by marked changes in the expression and presentation of various macromolecules at the cell surface. These tumor-associated adjustments result from the differential expression of genes coding for the production or post-translational modifications of these macromolecules during transformation to a particular tumor phenotype. In turn, tumor cells acquire distinct biophysical properties whic Read More