title: Plk1 Inhibitors in Cancer Therapy: From Laboratory to Clinics.
abstract: Polo-like kinase 1 (Plk1) overexpression has been shown to occur in a wide range of tumors, prompting research and development of Plk1 inhibitors as a means of cancer treatment. This review discusses recent advances in the development of Plk1 inhibitors for cancer management. Plk1 inhibition has been shown to cause mitotic block and apoptosis of cells with higher mitotic index and therefore higher Plk1 expression. The potential of Plk1 inhibitors as cancer therapeutics has been widely investigated. However, a complete understanding of Plk1 biology/mechanism is yet to be fully achieved. Resistance to certain chemotherapeutic drugs has been linked to Plk1 overexpression, and Plk1-mediated mitotic events such as microtubule rearrangement have been found to reduce the efficacy of chemotherapeutic agents. The Plk1 inhibitor volasertib has shown considerable promise in clinical studies, having reached phase III trials. However, preclinical success with Plk1 inhibitors has not translated well into clinical success. In our view, combined therapies targeting other relevant pathways together with Plk1 may be vital to combat issues observed with monotherapy, especially resistance. In addition, research should also be directed toward understanding the mechanisms of Plk1 and designing additional next generations of specific, potent Plk1 inhibitors to target cancer. Mol Cancer Ther; 15(7); 1427-35. ©2016 AACR.
authors.affiliation: Department of Dermatology, University of Wisconsin, Madison, Wisconsin.
authors.forename: Rosie Elizabeth Ann
authors.initials: RE
authors.lastname: Gutteridge
authors.affiliation: Department of Dermatology, University of Wisconsin, Madison, Wisconsin.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Ndiaye
authors.affiliation: Department of Biochemistry, Purdue University, West Lafayette, Indiana.
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Dermatology, University of Wisconsin, Madison, Wisconsin. William S. Middleton Memorial VA Hospital, Madison, Wisconsin. nahmad@wisc.edu.
authors.forename: Nihal
authors.initials: N
authors.lastname: Ahmad
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors*; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects; D057170:Translational Research, Biomedical; D016896:Treatment Outcome; D000097869:Polo-Like Kinase 1
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1