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Pelareorep + gemcitabine + cisplatin is a combination therapy comprising the oncolytic reovirus pelareorep and the cytotoxic chemotherapeutic agents gemcitabine and cisplatin. Pelareorep (Reolysin) is an unmodified, naturally occurring, non-enveloped, double-stranded RNA reovirus (Type 3 Dearing strain) that selectively replicates in and induces apoptosis in cancer cells with activated Ras signaling pathways, which are prevalent in many solid tumors. Gemcitabine is a nucleoside analog that inhibits DNA synthesis by inhibiting ribonucleotide reductase and competing for incorporation into DNA. Cisplatin is a platinum-based antineoplastic agent that forms intra-strand and inter-strand DNA cross-links, leading to the inhibition of DNA replication and transcription. The rationale for this combination is that pelareorep-induced viral oncolysis can act synergistically with chemotherapy to enhance tumor cell death and promote an immunogenic environment, potentially overcoming resistance to standard-of-care regimens. This triplet has been evaluated in Phase 2 clinical trials for advanced cancers, specifically targeting pancreatic adenocarcinoma and biliary tract cancers.
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