Hsp90: A Novel Target for the Disruption of Multiple Signaling Cascades
Stephanie C. Bishop, Joseph A. Burlison and Brian S. J. Blagg
Pages 369-388 (20)
The 90 kDa heat shock proteins (Hsp90) are proving to be an excellent target for the development of novel anticancer agents designed to selectively block the growth and proliferation of tumor cells. Since Hsp90 is a molecular chaperone and is responsible for folding numerous oncogenic proteins, its inhibition represents a novel approach toward the simultaneous disruption of multiple signaling cascades. This review summarizes recent literature implicating Hsp90 as a key facilitator for the maturation of proteins represented in all six hallmarks of cancer: 1) growth signal self-sufficiency, 2) anti-growth signal insensitivity, 3) evasion of apoptosis, 4) unlimited replicative potential, 5) metastasis and tissue invasion, and 6) sustained angiogenesis. Also described are recent advances towards the development of novel Hsp90 inhibitors via structure-based drug design that have contributed to the number of compounds undergoing clinical development.
Hsp90, heat shock protein, cancer, inhibitor, molecular chaperone, protein folding, geldanamycin, radicicol
Departments of Molecular Biosciences and Medicinal Chemistry, The University of Kansas, Lawrence, Kansas 66045-7563, USA.