fig5

Figure 5. Therapeutic strategies targeting ADSL-driven purine metabolism in PDAC. This schematic summarizes translational strategies for targeting ADSL-associated metabolic vulnerabilities. Four complementary approaches are shown: (A) direct or tumor-selective ADSL inhibition; (B) rational combination therapy targeting purine salvage, DDR pathways, redox adaptation, or chemotherapy resistance; (C) biomarker-guided patient selection using ADSL expression and purine-metabolic features; and (D) immunotherapeutic integration through modulation of innate immune signaling, including the cGAS–STING axis. ADSL: Adenylosuccinate lyase; PDAC: pancreatic ductal adenocarcinoma; DDR: DNA damage response; cGAS–STING: cyclic GMP-AMP synthase–stimulator of interferon genes; SAICAR: succinylaminoimidazole carboxamide ribotide; AICAR: aminoimidazole carboxamide ribotide; AMP: adenosine monophosphate; ROS: reactive oxygen species; IFNs: interferons.