[Akt enzyme: new therapeutic target in cancer and diabetes?].
Alteration of apoptotic processes plays a central role in the development and progression of several chronic disorders. Proteins responsible for the regulation of apoptosis are therapeutic targets; these include the Akt enzyme. Akt enzyme is expressed in most cell types. Akt activation is regulated by growth factors, insulin, and also environmental factors as altered oxygen tension and high temperature. Akt is a central regulator of cellular metabolism and survival. Akt function is reportedly altered in some disorders. An increased activity of Akt has been described in prostate, breast, colon, and pancreatic cancer, as well as in hematological malignancies. Akt is also a factor in the pathomechanism of diabetes as it determines beta-cell apoptosis of Langerhans islets and insulin sensitivity of the cells. Several studies revealed that some of the marketed drugs including statins, thiazolidinediones and ACE inhibitors modulate Akt activity. There are efforts to develop specific Akt inhibitors that may improve the efficacy of chemotherapy. Triciribine and perifosine are two Akt inhibitors in developmental phase 1 and 2 that may improve survival in breast cancer, pancreas cancer, gastrointestinal stroma tumor, sarcoma and melanoma, and in hematological malignancy.
Cseh
Aron
A
Semmelweis Egyetem, Altalános Orvostudományi Kar I. Gyermekgyógyászati Klinika Budapest Bókay u. 54. 1083, Hungary. sceharon@gmail.com
Szebeni
Beáta
B
Szalay
Balázs
B
Vásárhelyi
Barna
B
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis; D002465:Cell Movement; D049109:Cell Proliferation; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007333:Insulin Resistance; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism*; D012263:Ribonucleosides / Q000627:therapeutic use
D000970:Antineoplastic Agents; D007004:Hypoglycemic Agents; D012263:Ribonucleosides; D010767:Phosphorylcholine; C023764:triciribine; C105905:perifosine; D051057:Proto-Oncogene Proteins c-akt