title: Targeting tumour-supportive cellular machineries in anticancer drug development.
abstract: Traditional anticancer chemotherapeutics targeting DNA replication and cell division have severe side effects, but they have proved to be highly successful in treating some cancers. Drugs targeting signalling oncoproteins that have gained tumour-driving functions through mutations or overexpression were subsequently developed to increase specificity and thus reduce side effects, but have limitations such as the development of resistance. Now, a new wave of small-molecule anticancer agents is emerging, targeting complex multicomponent cellular machineries - including chromatin modifiers, heat shock protein chaperones and the proteasome - which thus interfere with those support systems that are more essential for cancer cells than for normal cells. Here, we provide our perspective on the advantages and limitations of agents that target tumour-supportive cellular machineries (other than those involving DNA replication), comparing them with agents that target signalling intermediates.
authors.affiliation: Institute of Molecular Oncology, Göttingen Center of Molecular Biosciences, Ernst Caspari Haus, University Medical Center Göttingen, 37077 Göttingen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Dobbelstein
authors.affiliation: 1] Institute of Molecular Oncology, Göttingen Center of Molecular Biosciences, Ernst Caspari Haus, University Medical Center Göttingen, 37077 Göttingen, Germany. [2] Department of Pathology, School of Medicine, Stony Brook University, Stony Brook, New York 11794, USA.
authors.forename: Ute
authors.initials: U
authors.lastname: Moll
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods* / Q000639:trends; D055808:Drug Discovery / Q000379:methods / Q000639:trends; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D002843:Chromatin; D006360:Heat-Shock Proteins