Differential expression of cell adhesion genes: implications for drug resistance.
It is well known that tumors arising from tissues such as kidney, pancreas, liver and stomach are particularly refractory to treatment. Searching for new anticancer drugs using cells in culture has yielded some effective therapies, but these refractory tumors remain intractable. Studies that compare cells grown in suspension to similar cells grown attached to one another as aggregates have suggested that it is adhesion to the extracellular matrix of the basal membrane that confers resistance to apoptosis and, hence, resistance to cytotoxins. The genes whose expression correlates with poor survival might, therefore, act through such a matrix-to-cell suppression of apoptosis. Indeed, correlative mining of gene expression and patient survival databases suggests that poor survival in patients with metastatic cancer correlates highly with tumor expression of a common theme: the genes involved in cell adhesion and the cytoskeleton. If the proteins involved in tethering cells to the extracellular matrix are important in conferring drug resistance, it may be possible to improve chemotherapy by designing drugs that target these proteins.
Stein
Wilfred D
WD
Silberman Institute of Life Sciences, Hebrew University, Jerusalem, Israel. wdstein@vms.huji.ac.il
Litman
Thomas
T
Fojo
Tito
T
Bates
Susan E
SE
D000970:Antineoplastic Agents / Q000627:therapeutic use; D002448:Cell Adhesion / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis
D000970:Antineoplastic Agents