title: Heat shock protein and proteasome targeting agents.
abstract: Proteasome inhibitors such as PS-341 are novel agents with great potential as anticancer drugs. In early clinical studies, PS-341 was tolerated well with promising evidence of antitumor activity in diseases such as multiple myeloma. Studies also are ongoing in solid tumors, as single agent therapy and in combination with standard agents such as carboplatin. Although more research is needed to clarify the precise spectrum of antitumor activity of proteasome inhibitors, this novel approach to targeting human malignancies is highly promising.
authors.affiliation: Department of Medicine, Division of Medical Oncology, University of Texas Health Science Center at San Antonio, Institute for Drug Development, Cancer Therapy and Research Center, San Antonio, TX 78229, USA. takimoto@uthscsa.edu
authors.forename: Chris H
authors.initials: CH
authors.lastname: Takimoto
authors.forename: Shrinivas
authors.initials: S
authors.lastname: Diggikar
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016227:Benzoquinones; D017321:Clinical Trials, Phase I as Topic; D003546:Cysteine Endopeptidases / Q000502:physiology*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D047029:Lactams, Macrocyclic; D051379:Mice; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000502:physiology*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000188:drug therapy; D011480:Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D046988:Proteasome Endopeptidase Complex; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011809:Quinones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D017828:Rifabutin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D025801:Ubiquitin / Q000037:antagonists & inhibitors / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D011480:Protease Inhibitors; D011809:Quinones; D025801:Ubiquitin; D017828:Rifabutin; C112765:tanespimycin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C001277:geldanamycin