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Solute carrier family 68 member 1 (TMEM180) is a multi-pass transmembrane protein that functions as a cation symporter, primarily involved in the uptake and metabolism of essential amino acids such as glutamine and arginine (UniProt Q14CX5; Anzai et al., 2021). It is highly and specifically expressed in colorectal cancer (CRC) cells, as well as in breast and ovarian cancers, while remaining virtually undetectable in normal tissues (Yasunaga et al., 2019; Shiraishi et al., 2021). The expression of TMEM180 is significantly upregulated under hypoxic conditions, a hallmark of the tumor microenvironment, and the protein is also found on the surface of tumor-derived exosomes (Yasunaga et al., 2019). By facilitating the transport of nutrients required for rapid cell division, TMEM180 plays a critical role in promoting cancer cell proliferation and tumor growth (Anzai et al., 2021). Due to its high tumor specificity and its role in cancer metabolism, it has emerged as a promising therapeutic target for antibody-based therapies (Yasunaga et al., 2019). Humanized monoclonal antibodies targeting TMEM180 have demonstrated potent antitumor activity in preclinical models through mechanisms such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) (Yasunaga et al., 2019). A Phase 1 clinical trial for a lead anti-TMEM180 antibody candidate is currently underway, highlighting its potential as a novel precision medicine for CRC patients (RIN Institute, 2023).
Antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antibody-dependent cellular phagocytosis (ADCP)
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