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**siG12D-LODER + gemcitabine + nab-paclitaxel** is an investigational combination regimen for locally advanced pancreatic cancer (LAPC). - **siG12D-LODER** is a miniature biodegradable polymeric implant delivering a small interfering RNA (siRNA) targeting the KRAS G12D mutation; it is designed to be locally implanted in the tumor and release the siRNA over several months, inhibiting KRAS-driven tumor proliferation[1][5][6]. - **Gemcitabine** is a nucleoside analog, a cytotoxic small molecule chemotherapy that inhibits DNA synthesis. - **Nab-paclitaxel** (nanoparticle albumin-bound paclitaxel; Abraxane) is a microtubule inhibitor formulated as albumin-bound nanoparticles to improve delivery and reduce toxicity. The combination aims to exploit molecular targeting of KRAS G12D mutations (common in pancreatic adenocarcinoma) while maintaining the cytotoxic effects of chemotherapy to maximize efficacy in LAPC[5][6]. In phase 1/2 clinical studies, this regimen has demonstrated safety and potential efficacy, including durable disease control and signs of tumor response[1][6].
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