Project Grant R41CA285174

A NOVEL DUAL-CARRIER ULTRASMALL NANOMEDICINE FOR THE TREATMENT OF STROMA-RICH PANCREATIC CANCER - ABSTRACT PANCREATIC CANCER (PC) HAS AN ANNUAL WORLDWIDE INCIDENCE OF MORE THAN 495,000 CASES AND AN ANNUAL MORTALITY RATE OF ALMOST 460,000 CASES. MOST PATIENTS ARE DIAGNOSED LATE AND CANNOT UNDERGO RESECTION AND THEREFORE RELY ON PHARMACOTHERAPY TO EXTEND THEIR LIVES. CURRENT THERAPIES OFFER ONLY LIMITED BENEFIT DUE IN LARGE PART TO THE DENSE STROMA TISSUE THAT SURROUNDS AND PROTECTS THE TUMOR. DUO ONCOLOGY IS DEVELOPING AN ULTRA-SMALL NANOPARTICLE CONTAINING, GEMCITABINE AND AN IMMUNOMODULATORY CHEMOKINE RECEPTOR TYPE 2 ANTAGONIST TO KILL CANCER CELLS AND INVIGORATE ANTI-TUMOR IMMUNITY. THESE SMALL NANOPARTICLES, LESS THAN 30NM IN DIAMETER, SHOW ENHANCED EXTRAVASATION AND TISSUE PENETRATION, PARTICULARLY IN THE PC TUMORS ENRICHED WITH DENSE STROMA. FURTHER, RESEARCH PROPOSED HEREIN WILL PREPARE DUO-307 FOR FUTURE IND-ENABLING STUDIES WITH FORMULATION OPTIMIZATION, TOXICOLOGY, AND THERAPEUTIC EFFICACY USING A CUTTING EDGE EX VIVO TUMOR EXPLANT MODEL AND A CLINICALLY-RELEVANT MOUSE MODEL OF PC WITH DENSE STROMA.