Tubulin-associated proteins: Aurora and Polo-like kinases as therapeutic targets in cancer.
Tubulin is a very important target for cancer-fighting therapies; therefore, the cancer research community continues to adopt new ways of developing the therapeutic potential of tubulin and tubulin-associated proteins. Two families of tubulin-associated kinases, Aurora and Polo-like, have received significant attention regarding how they contribute to tumorigenesis and can be targeted with selective small molecule inhibitors. Aurora and Polo-like kinases play essential roles in centrosome separation, chromosome alignment and segregation, and cytokinesis. Inhibition of any of these kinases results in abnormal mitotic events (which vary depending on the particular family member) and eventually leads to apoptosis. Because of the biological consequences of inhibiting these kinases, several Aurora or Polo-like selective inhibitors have advanced to various stages of preclinical and clinical development; the most advanced are currently in phase 2 clinical trials.
Warner
Steven L
SL
Translational Research Division, Translational Genomics Research Institute, 445 North Fifth Street, Phoenix, AZ 85004, USA.
Stephens
Bret J
BJ
Von Hoff
Daniel D
DD
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000502:physiology*; D002875:Chromosomes / Q000648:ultrastructure; D002986:Clinical Trials as Topic; D048749:Cytokinesis; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009369:Neoplasms / Q000201:enzymology* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D014404:Tubulin / Q000502:physiology*; D000097869:Polo-Like Kinase 1
D000970:Antineoplastic Agents; D064127:Aurora Kinases; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D014404:Tubulin; D000097869:Polo-Like Kinase 1