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Nerofe + doxorubicin is a combination therapy consisting of Nerofe (a derivative of the hormone peptide Tumor Cell Apoptosis Factor, abbreviated dTCApFs) and doxorubicin, a well-established anthracycline chemotherapy agent. This combination is studied primarily for KRAS-mutated and ST2-positive advanced solid tumors, such as metastatic colorectal cancer. Nerofe acts by targeting the T1/ST2 receptor, which is overexpressed in various cancers, and induces endoplasmic reticulum (ER) stress leading to apoptosis. Doxorubicin inhibits the unfolded protein response and increases reactive oxygen species, facilitating cell death. Together, they synergistically downregulate KRAS and MAPK1/2 pathways via miR217 upregulation, resulting in enhanced tumor cell apoptosis and activation of both innate (NK cells, M1 macrophages) and adaptive (IL-2, IFN-γ) immune responses. This dual approach leverages direct cytotoxicity and immunostimulation for improved antitumor efficacy[1][3][6].
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