title: Targeting WEE1 Kinase in Cancer.
abstract: WEE1 kinase plays a crucial role in the G2-M cell-cycle checkpoint arrest for DNA repair before mitotic entry. Normal cells repair damaged DNA during G1 arrest; however, cancer cells often have a deficient G1-S checkpoint and depend on a functional G2-M checkpoint for DNA repair. WEE1 is expressed at high levels in various cancer types including breast cancers, leukemia, melanoma, and adult and pediatric brain tumors. Many of these cancers are treated with DNA-damaging agents; therefore, targeting WEE1 for inhibition and compromising the G2-M checkpoint presents an opportunity to potentiate therapy. In this review we summarize the current WEE1 inhibitors, the potential for further inhibitor development, and the challenges in the clinic for the WEE1 inhibitor strategy.
authors.affiliation: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, 12850 East Montview Boulevard, V20-2102, Aurora, CO 80045, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Matheson
authors.affiliation: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, 12850 East Montview Boulevard, V20-2102, Aurora, CO 80045, USA.
authors.forename: Donald S
authors.initials: DS
authors.lastname: Backos
authors.affiliation: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, 12850 East Montview Boulevard, V20-2102, Aurora, CO 80045, USA. Electronic address: philipreigan@ucdenver.edu.
authors.forename: Philip
authors.initials: P
authors.lastname: Reigan
mesh_terms: D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002648:Child; D004260:DNA Repair / Q000187:drug effects; D015195:Drug Design; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; C499349:WEE1 protein, human
keywords: DNA-damaging agents; Wee1; combination therapy; inhibitor; kinase