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TXN10128 + irinotecan is a combination investigational regimen being evaluated in phase I clinical trials for the treatment of locally advanced (unresectable) or metastatic solid tumors, including colorectal cancer[1][5]. **TXN10128** is a small molecule inhibitor of **ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase 1)**, an enzyme that hydrolyzes cGAMP, thereby attenuating STING pathway activation and anti-tumor immune responses within the tumor microenvironment. By inhibiting ENPP1, TXN10128 restores STING signaling, increases infiltration and activity of immune cells (NK cells and dendritic cells), converting immunologically "cold" tumors into "hot" tumors to augment anti-tumor immunity[5][7][8]. **Irinotecan** is a topoisomerase I inhibitor, commonly used as chemotherapy in solid tumors; it induces cytotoxicity via inhibition of DNA replication in rapidly dividing cancer cells. The combination is designed to offer both direct cytotoxic and immunomodulatory effects by leveraging irinotecan’s DNA-damaging action and TXN10128’s immune-enhancing properties.
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