Inhibition of Aberrantly Overexpressed Polo-like Kinase 4 Is a Potential Effective Treatment for DNA Damage Repair-Deficient Uterine Leiomyosarcoma

• Published in: Clinical cancer research Vol. 30; no. 17; pp. 3904 - 3918
• Main Authors: Lee, Horace H Y, Chow, Kin Long, Wong, Ho Shing, Chong, Tsz Yan, Wong, Alice S T, Cheng, Grace H W, Ko, Jasmine M K, Siu, Hoi Cheong, Yeung, Maximus C F, Huen, Michael S Y, Tse, Ka Yu, Bray, Mark R, Mak, Tak Wah, Leung, Suet Yi, Ip, Philip P C
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research 03.09.2024
• Subjects: Animals; Ataxia Telangiectasia Mutated Proteins - antagonists & inhibitors; Ataxia Telangiectasia Mutated Proteins - genetics; Biomarkers; Cell Line, Tumor; DNA Damage - drug effects; DNA Repair - drug effects; Female; Gene Expression Regulation, Neoplastic - drug effects; Gynecological Cancers; Humans; Indoles - pharmacology; Indoles - therapeutic use; Leiomyosarcoma - drug therapy; Leiomyosarcoma - genetics; Leiomyosarcoma - pathology; Mice; Morpholines - pharmacology; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Protein Serine-Threonine Kinases - antagonists & inhibitors; Protein Serine-Threonine Kinases - genetics; Pyridines; Quinolines; Translational Cancer Mechanisms and Therapy; Translational Research; Uterine Neoplasms - drug therapy; Uterine Neoplasms - genetics; Uterine Neoplasms - pathology; Xenograft Model Antitumor Assays

Uterine leiomyosarcoma (LMS) is an aggressive sarcoma and a subset of which exhibits DNA repair defects. Polo-like kinase 4 (PLK4) precisely modulates mitosis, and its inhibition causes chromosome missegregation and increased DNA damage. We hypothesize that PLK4 inhibition is an effective LMS treatm...