title: Polo-like kinase inhibitors in hematologic malignancies.
abstract: Polo-like kinases (Plk) are key regulators of the cell cycle and multiple aspects of mitosis. Two agents that inhibit the Plk signaling pathway have shown promising activity in patients with hematologic malignancies and are currently in phase III trials. Volasertib is a Plk inhibitor under evaluation combined with low-dose cytarabine in older patients with acute myeloid leukemia (AML) ineligible for intensive induction therapy. Rigosertib, a dual inhibitor of the Plk and phosphatidylinositol 3-kinase pathways, is under investigation in patients with myelodysplastic syndrome (MDS) who have failed azacitidine or decitabine treatment. The prognosis for patients with AML, who are ineligible for intensive induction therapy, and for those with MDS refractory/relapsed after a hypomethylating agent, remains poor. Novel approaches, such as Plk inhibitors, are urgently needed for these patients. Here, we provide a comprehensive overview of the current state of development of Plk inhibitors for the treatment of hematologic malignancies.
authors.affiliation: Leukemia Section, Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA. Electronic address: Chetasi.Talati@RoswellPark.org.
authors.forename: Chetasi
authors.initials: C
authors.lastname: Talati
authors.affiliation: Leukemia Section, Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA. Electronic address: Elizabeth.Griffiths@RoswellPark.org.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Griffiths
authors.affiliation: Leukemia Section, Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
authors.forename: Meir
authors.initials: M
authors.lastname: Wetzler
authors.affiliation: Leukemia Section, Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA. Electronic address: Eunice.Wang@RoswellPark.org.
authors.forename: Eunice S
authors.initials: ES
authors.lastname: Wang
mesh_terms: D010129:4-Aminobenzoic Acid / Q000627:therapeutic use; D001381:Azepines / Q000627:therapeutic use; D001552:Benzazepines / Q000627:therapeutic use; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors*; D017326:Clinical Trials, Phase III as Topic; D005998:Glycine / Q000031:analogs & derivatives / Q000627:therapeutic use; D019337:Hematologic Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors*; D011621:Pteridines / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D013450:Sulfones / Q000627:therapeutic use; D013871:Thiones / Q000627:therapeutic use; D000097869:Polo-Like Kinase 1
chemical_list: D010129:4-Aminobenzoic Acid; D001381:Azepines; D001552:Benzazepines; D018797:Cell Cycle Proteins; D005998:Glycine; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011621:Pteridines; D013450:Sulfones; D013871:Thiones; D000097869:Polo-Like Kinase 1; C573314:4-((9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido(4,5-b)(1,4)diazepin-2-yl)amino)-2-fluoro-5-methoxy-N-(1-methylpiperidin-4-yl)benzamide; C570910:9-trifluoromethyl-2-((5-(3-(dimethylamino)propyl)-2-methylpyridin-3-yl)amino)-5,7-dihydro-6H-pyrimido(5,4-d)(1)benzazepine-6-thione; C541363:BI 6727; C507134:ON 01910
keywords: Acute myeloid leukemia; Drug development; Myelodysplastic syndromes; Polo-like kinase