Clinical development of mammalian target of rapamycin inhibitors.
Rapamycin and CCI-779 have significant in vitro and in vivo anti-proliferative activity against a broad range of human tumor cell lines, justifying the clinical evaluation of this class of agent in cancer patients. Preliminary results from phase I studies of CCI-779 suggest that the agent is well tolerated and has anti-tumor activity. The challenge to investigators is to efficiently determine what role this class of agent will play in the treatment of cancer patients.
Dancey
Janet E
JE
Cancer Treatment Evaluation Program, Division of Cancer Treatment and Diagnosis, Investigational Drug Branch/CTEP/DCTD/NCI, 6130 Executive Boulevard, EPN 7131, Rockville, MD 20854, USA. danceyj@ctep.nci.nih.gov
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002352:Carrier Proteins / Q000502:physiology; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects; D002986:Clinical Trials as Topic; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D039642:Eukaryotic Initiation Factors; D000068338:Everolimus; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010750:Phosphoproteins / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases; D023041:Xenograft Model Antitumor Assays
D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D004791:Enzyme Inhibitors; D039642:Eukaryotic Initiation Factors; D000068338:Everolimus; D007166:Immunosuppressive Agents; D009363:Neoplasm Proteins; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; C087000:EIF4EBP1 protein, human; C499527:Eif4ebp1 protein, mouse; C401859:temsirolimus; C546842:MTOR protein, human; C546843:mTOR protein, mouse