Journal
LIFE SCIENCES
Volume 336, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2023.122294
Keywords
DCLK1; Targeted therapy; Immunotherapy; DNA repair; Metastasis; Stemness
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Doublecortin-like kinase 1 (DCLK1) is a significant prooncogenic factor that is strongly associated with the malignant progression and clinical prognosis of various cancers. DCLK1 plays important roles in stem cell marker regulation, tumor cell reprogramming, and immune evasion. However, the exact biological functions of DCLK1, especially the disparities between its alpha- and beta-form transcripts in cancer progression, remain ambiguous.
Doublecortin-like kinase 1 (DCLK1), a significant constituent of the protein kinase superfamily and the doublecortin family, has been recognized as a prooncogenic factor that exhibits a strong association with the malignant progression and clinical prognosis of various cancers. DCLK1 serves as a stem cell marker that governs tumorigenesis, tumor cell reprogramming, and epithelial-mesenchymal transition. Multiple studies have indicated the capable of DCLK1 in regulating the DNA damage response and facilitating DNA damage repair. Additionally, DCLK1 is involved in the regulation of the immune microenvironment and the promotion of tumor immune evasion. Recently, DCLK1 has emerged as a promising therapeutic target for a multitude of cancers. Several small-molecule inhibitors of DCLK1 have been identified. Nevertheless, the biological roles of DCLK1 are mainly ambiguous, particularly with the disparities between its alpha- and beta-form transcripts in the malignant progression of cancers, which impedes the development of more precisely targeted drugs. This article focuses on tumor stem cells, tumor epithelial-mesenchymal transition, the DNA damage response, and the tumor microenvironment to provide a comprehensive overview of the association between DCLK1 and tumor malignant progression, address unsolved questions and current challenges, and project future directions for targeting DCLK1 for the diagnosis and treatment of cancers.
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