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This is a combination regimen consisting of three drugs: - **Sitagliptin** is a dipeptidyl peptidase-4 (DPP-4) inhibitor, primarily used as an oral antihyperglycemic agent in type 2 diabetes. In the context of cancer therapy, recent studies have shown that sitagliptin can induce degradation of ribonucleotide reductase subunits RRM1/RRM2 via the ubiquitin-proteasome pathway, leading to altered pyrimidine metabolism and alleviation of replication stress in tumor cells. - **Gemcitabine** is a nucleoside analog and antimetabolite chemotherapeutic agent that inhibits DNA synthesis by incorporating into DNA strands during replication, resulting in cell cycle arrest and apoptosis. - **Nab-paclitaxel** (nanoparticle albumin-bound paclitaxel) is a microtubule inhibitor formulated with albumin nanoparticles to enhance delivery; it disrupts microtubule function required for mitosis. The combination has been investigated for use in previously untreated advanced pancreatic ductal adenocarcinoma (PDAC). Preclinical data suggest that sitagliptin may synergistically enhance the efficacy of gemcitabine plus nab-paclitaxel by suppressing RRM1/RRM2-mediated pyrimidine metabolism. Early-phase clinical trial results indicate encouraging antitumor activity with manageable safety[1][2].
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