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Cisplatin + interferon alpha is a combination therapy consisting of the platinum-based chemotherapeutic agent cisplatin and the immunomodulatory cytokine interferon alpha. Cisplatin acts as an alkylating agent that cross-links DNA, leading to inhibition of DNA replication and transcription, ultimately causing cell death. Interferon alpha is a type I interferon with antiviral and immunomodulatory properties; it induces cell cycle arrest, apoptosis, autophagy, and enhances immune responses against tumor cells. The combination has been investigated for synergistic antitumor effects in various cancers including diffuse malignant pleural mesothelioma (DMPM), hepatocellular carcinoma (as part of PIAF regimen), pancreatic cancer, osteosarcoma, colon cancer models, and others. Mechanistically, this combination not only increases direct cytotoxicity but also modulates multidrug resistance proteins such as P-glycoprotein and MRP1/3 to restore chemosensitivity[1][2][6][9][10]. Clinical studies have shown efficacy at the expense of notable hematological toxicity.
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