Polo-like kinases and acute leukemia
| Autor: | Linda Vidarsdottir, Iryna Kolosenko, Caroline Palm-Apergi, Oksana Goroshchuk, Alireza Azimi |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Adult
0301 basic medicine PLK4 Cancer Research Antineoplastic Agents Cell Cycle Proteins Polo-like kinase Protein Serine-Threonine Kinases Biology PLK1 Gene Expression Regulation Enzymologic Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine RNA interference Proto-Oncogene Proteins Antineoplastic Combined Chemotherapy Protocols Genetics Animals Humans Molecular Targeted Therapy Child Protein Kinase Inhibitors Molecular Biology Clinical Trials as Topic Acute leukemia Leukemia Gene Expression Regulation Leukemic Kinase Tumor Suppressor Proteins Hematopoietic Stem Cell Transplantation Volasertib Combined Modality Therapy Neoplasm Proteins Survival Rate Clinical trial 030104 developmental biology chemistry Multigene Family 030220 oncology & carcinogenesis Acute Disease Cancer research RNA Interference Drug Screening Assays Antitumor |
| Zdroj: | Oncogene. 38:1-16 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/s41388-018-0443-5 |
| Popis: | Acute leukemia is a common malignancy among children and adults worldwide and many patients suffer from chronic health issues using current therapeutic approaches. Therefore, there is a great need for the development of novel and more specific therapies with fewer side effects. The family of Polo-like kinases (Plks) is a group of five serine/threonine kinases that play an important role in cell cycle regulation and are critical targets for therapeutic invention. Plk1 and Plk4 are novel targets for cancer therapy as leukemic cells often express higher levels than normal cells. In contrast, Plk2 and Plk3 are considered to be tumor suppressors. Several small molecule inhibitors have been developed for targeting Plk1 inhibition. Despite reaching phase III clinical trials, one of the ATP-competitive Plk1 inhibitor, volasertib, did not induce an objective clinical response and even caused lethal side effects in some patients. In order to improve the specificity of the Plk1 inhibitors and reduce off-target side effects, novel RNA interference (RNAi)-based therapies have been developed. In this review, we summarize the mechanisms of action of the Plk family members in acute leukemia, describe preclinical studies and clinical trials involving Plk-targeting drugs and discuss novel approaches in Plk targeting. |
| Databáze: | OpenAIRE |
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