Polo-like kinases and acute leukemia

• Published in: Oncogene Vol. 38; no. 1; pp. 1 - 16
• Main Authors: Goroshchuk, Oksana, Kolosenko, Iryna, Vidarsdottir, Linda, Azimi, Alireza, Palm-Apergi, Caroline
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 2019; Nature Publishing Group
• Subjects: 631/154/109; 631/154/1435; 631/154/152; 631/67/1990/283; 631/67/2332; Acute Disease; Acute leukemia; Adult; Animals; Antineoplastic agents; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Apoptosis; Cancer; Cancer research; Cancer treatment; Care and treatment; Cell Biology; Cell cycle; Cell Cycle Proteins - antagonists & inhibitors; Cell Cycle Proteins - genetics; Cell Cycle Proteins - physiology; Child; Children; Clinical trials; Clinical Trials as Topic; Combined Modality Therapy; Development and progression; Drug delivery; Drug Screening Assays, Antitumor; Gene expression; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Leukemic; Genetic aspects; Health; Health aspects; Hematopoietic Stem Cell Transplantation; Human Genetics; Humans; Internal Medicine; Leukemia; Leukemia - drug therapy; Leukemia - enzymology; Leukemia - therapy; Malignancy; Medical research; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Mice; Molecular Targeted Therapy; Multigene Family; Neoplasm Proteins - antagonists & inhibitors; Neoplasm Proteins - physiology; Oncology; Phosphotransferases; Polo; Polo-Like Kinase 1; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Protein Serine-Threonine Kinases - antagonists & inhibitors; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - physiology; Proto-Oncogene Proteins - antagonists & inhibitors; Review Article; RNA; RNA Interference; RNA-mediated interference; Serine; Side effects; Survival Rate; Threonine; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - physiology; Tumors
• ISSN: 0950-9232; 1476-5594; 1476-5594
• DOI: 10.1038/s41388-018-0443-5

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.