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Cytoskeleton-associated protein 5 (CKAP5), also known as ch-TOG (colonic and hepatic tumor overexpressed gene), is a large microtubule-associated protein that functions as a microtubule polymerase, essential for the growth of microtubule plus-ends (UniProt, 2024; Gergely et al., 2003). It plays a critical role in spindle assembly, centrosome stability, and the regulation of mitosis (Cassimeris & Morabito, 2004). While typically localized within the cytoplasm and at the centrosomes, CKAP5 has been identified as being expressed on the cell surface of certain malignant cells, including those in hepatocellular carcinoma (HCC) (Zhang et al., 2021; Charrasse et al., 1998). This aberrant surface localization in cancer cells makes it a viable target for antibody-drug conjugates (ADCs), which can selectively deliver cytotoxic agents to tumor cells while sparing normal cells where the protein remains intracellular (Wang et al., 2022; Zhang et al., 2021). Overexpression of CKAP5 in hepatocytes is often associated with advanced disease stages and poor prognosis, positioning it as both a valuable biomarker and a promising therapeutic target in oncology (Charrasse et al., 1998; Wang et al., 2022). Experimental therapies targeting surface CKAP5 aim to exploit this differential localization to improve the therapeutic index of microtubule-disrupting agents (Zhang et al., 2021).
Targeted delivery of cytotoxic payloads via antibody-mediated internalization; inhibition of microtubule polymerization leading to mitotic arrest.
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