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Antigen KI-67 is a large nuclear protein that is strictly associated with cell proliferation and is expressed during all active phases of the cell cycle (G1, S, G2, and mitosis) but is absent from resting cells in the G0 phase [1, 2]. Biologically, it acts as a biological surfactant, maintaining the individual integrity of mitotic chromosomes and preventing them from collapsing into a single chromatin mass after nuclear envelope breakdown [3]. In clinical oncology, the Ki-67 labeling index is widely utilized as a prognostic and predictive biomarker to assess tumor aggressiveness and response to therapy, particularly in breast, lung, and neuroendocrine cancers [5]. While primarily used for diagnostics, Ki-67 is also being explored as a therapeutic target using antisense oligonucleotides and siRNA to inhibit tumor growth by inducing cell cycle arrest [4]. However, because it is essential for the proliferation of normal cells, achieving a therapeutic window and effective delivery remain significant challenges for drug development. [1] UniProt (P46013); [2] NCBI Gene (4288); [3] Cuylen et al. (2016) Nature 535:308-312; [4] Li et al. (2015) Mol Med Rep 11(4):2439-2444; [5] Nielsen et al. (2020) JNCI 113(7):808-819.
Binding to the Ki-67 protein for immunohistochemical detection in diagnostic applications; antisense-mediated knockdown of MKI67 mRNA to inhibit protein synthesis and induce cell cycle arrest in experimental therapeutic contexts.
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