Over the years, polo-like kinase 1 (PLK1) has garnered great interest as a therapeutic target. The PLK1 is a member of a highly conserved serine/threonine kinase family that plays pivotal roles in mitosis, cytokinesis and DNA damage response in eukaryotic cells. In this review, we summarize the functions of PLK1 during cell cycle progression, its roles in human pediatric cancer and its value as a prognostic factor. Furthermore, we introduce the advances in pharmacological inhibition and the newly chemotherapeutic development of small-molecules to target PLK1 in cancer treatment. Finally, clinical trials with PLK1 inhibitors are briefly reviewed.
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http://dx.doi.org/10.2174/1389450116666150825120235 | DOI Listing |
Int J Mol Sci
January 2025
Laboratory of Gynecological Preclinical Oncology, Department of Experimental Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy.
Mucinous epithelial ovarian cancer (mEOC) is a rare subtype of epithelial ovarian cancer, characterized by poor responses to standard platinum-based chemotherapy. Polo-like kinase 1 (PLK1) is a key regulator of mitosis and cell cycle progression and its inhibition has been recently identified as a target in mEOC. In this study, we aimed to identify further therapeutic targets in mEOC using a CRISPR/Cas9 library targeting 3015 genes, with and without treatment with onvansertib, a PLK1 inhibitor.
View Article and Find Full Text PDFBiomedicines
December 2024
Institute of Clinical Pathology and Cytology, Merkur University Hospital, 10000 Zagreb, Croatia.
: Early-onset colorectal cancer (EOCRC) is more frequently characterized by poorly differentiated, aggressive tumors, often diagnosed at advanced stages, and associated with worse prognoses. Despite these differences, current treatment guidelines do not distinguish between EOCRC and late-onset colorectal cancer (LOCRC). Elevated expression of polo-like kinase 1 (PLK-1) has been linked to advanced disease stages and poorer treatment outcomes, including resistance to both chemotherapy and radiotherapy.
View Article and Find Full Text PDFJ Med Chem
January 2025
State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China.
Blocking mitosis is a promising strategy to induce tumor cell death. However, AMPK- and PFKFB3-mediated glycolysis can maintain ATP supply and help tumor cells overcome antimitotic drugs. Inhibiting glycolysis provides an opportunity to decrease the resistance of tumor cells to antimitotic drugs.
View Article and Find Full Text PDFAm J Clin Exp Urol
December 2024
Department of Urology, General Hospital of Northern Theater Command Shenyang 110016, Liaoning, China.
Objective: To investigate the expression of metabolism-related genes (MRGs) in kidney renal clear cell carcinoma (KIRC) and their association with patient prognosis, and to identify potential targets for intervention.
Methods: Bioinformatics methods were employed to mine the KIRC transcriptome data in The Cancer Genome Atlas Program (TCGA) database in order to identify MRGs that are aberrantly expressed in cancerous tissues. Subsequently, a prognostic risk score model was constructed and its predictive capacity was evaluated.
Cancer Res Commun
January 2025
Indiana University School of Medicine, Bloomington, IN, United States.
Ovarian cancer is a deadly gynecological disease with frequent recurrence. Current treatments for patients include platinum-based therapy regimens with PARP inhibitors specific for HR-deficient high-grade serous ovarian cancers (HGSOCs). Despite initial effectiveness, patients inevitably develop disease progression as tumor cells acquire resistance.
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