Emerging cancer therapeutic opportunities by inhibiting mitotic kinases.
Among cellular kinases, several cell cycle protein kinases play critical roles in mitotic entry and chromosome segregation. Inhibition of these proteins frequently results in dramatic mitotic arrest and subsequent apoptosis. Most drug discovery efforts have been directed against members of the cyclin-dependent kinase (CDK), Aurora and Polo-like kinase families. Inhibition of these proteins with small molecules has emerged as a powerful research tool and their clinical use is currently being tested in phase I and phase II trials for cancer therapy. New unexplored kinases or new protein domains distinct to the kinase pocket are now being evaluated for the next generation of mitotic drugs. The therapeutic value of inhibiting these kinases will improve with the availability of new specific and potent inhibitors, but it will also rely on a better knowledge of the physiological requirement for these proteins in normal and tumor cell cycles.
Pérez de Castro
Ignacio
I
Cell Division and Cancer Group, Centro Nacional de Investigaciones Oncológicas (CNIO), Melchor Fernández Almagro 3, Madrid, Spain.
de Cárcer
Guillermo
G
Montoya
Guillermo
G
Malumbres
Marcos
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D064127:Aurora Kinases; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D018816:Genes, cdc / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D008941:Spindle Apparatus / Q000187:drug effects / Q000201:enzymology*
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase