title: Expression, adverse prognostic significance and therapeutic small molecule inhibition of Polo-like kinase 1 in multiple myeloma.
abstract: The amplified myeloma centrosome has been identified as a therapeutic target. The present study explored the expression and prognostic significance of the centrosome-associated protein PLK1 in myeloma and the effect of BI 2536, a potent and selective inhibitor of PLK1, on myeloma cells. High plasma cell expression of PLK1 protein in myeloma patient bone marrow biopsies is an independent adverse prognostic factor (HR=2.3, p=0.003 unadjusted; HR=1.9, p=0.03 in multivariable model). BI 2536 inhibits myeloma cell lines at nanomolar concentrations, and is therapeutic for xenografts in NOD/SCID mice. PLK1 inhibition is a potential new strategy for the treatment of multiple myeloma.
authors.affiliation: Department of Oncology; Saint John Regional Hospital, Saint John, NB, Canada.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Evans
authors.forename: Greg
authors.initials: G
authors.lastname: Dueck
authors.forename: Roger
authors.initials: R
authors.lastname: Sidhu
authors.forename: Sunita
authors.initials: S
authors.lastname: Ghosh
authors.forename: Inka
authors.initials: I
authors.lastname: Toman
authors.forename: Jonathan
authors.initials: J
authors.lastname: Loree
authors.forename: Nizar
authors.initials: N
authors.lastname: Bahlis
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Klimowicz
authors.forename: Joyce
authors.initials: J
authors.lastname: Fung
authors.forename: Michelle
authors.initials: M
authors.lastname: Jung
authors.forename: Raymond
authors.initials: R
authors.lastname: Lai
authors.forename: Linda M
authors.initials: LM
authors.lastname: Pilarski
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Belch
authors.forename: Tony
authors.initials: T
authors.lastname: Reiman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D000097869:Polo-Like Kinase 1
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D054852:Small Molecule Libraries; D000097869:Polo-Like Kinase 1