title: Hitting the brakes: targeting microtubule motors in cancer.
abstract: Despite the growing number of therapies that target cancer-specific pathways, cytotoxic treatments remain important clinical tools. The rationale for targeting cell proliferation by chemotherapeutic agents stems from the assumption that tumours harbour a greater fraction of actively dividing cells than normal tissues. One such group of cytotoxic drugs impair microtubule polymers, which are cytoskeletal components of cells essential for many processes including mitosis. However, in addition to their antimitotic action, these agents cause debilitating and dose-limiting neurotoxicity because of the essential functions of microtubules in neurons. To overcome this limitation, drugs against mitosis-specific targets have been developed over the past decade, albeit with variable clinical success. Here we review the key lessons learnt from antimitotic therapies with a focus on inhibitors of microtubule motor proteins. Furthermore, based on the cancer genome data, we describe a number of motor proteins with tumour type-specific alterations, which warrant further investigation in the quest for cytotoxic targets with increased cancer specificity.
authors.affiliation: Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Robinson Way, Cambridge CB2 0RE, UK.
authors.forename: Gayathri
authors.initials: G
authors.lastname: Chandrasekaran
authors.affiliation: Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Robinson Way, Cambridge CB2 0RE, UK.
authors.forename: Péter
authors.initials: P
authors.lastname: Tátrai
authors.affiliation: Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Robinson Way, Cambridge CB2 0RE, UK.
authors.forename: Fanni
authors.initials: F
authors.lastname: Gergely
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D016547:Kinesins / Q000037:antagonists & inhibitors / Q000502:physiology; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy*; D050257:Tubulin Modulators / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D050257:Tubulin Modulators; D016547:Kinesins