Cascade-Targeted Nanoparticles for Enhanced Gemcitabine Delivery and Adenosine Metabolism Modulation to Overcome Treatment Resistance in Pancreatic Cancer.

ABSTRACT: KRAS mutations are find in over 90% of pancreatic ductal adenocarcinoma (PDAC) cases, making PDAC exhibit intrinsic resistance to chemotherapy and reshape the immunosuppressive tumor microenvironment (TME), disappointing the clinically preferred chemotherapy-immunotherapy combination. Standing on the cross point of therapeutic resistance, the aberrant adenosine metabolism contributes greatly to chemo- and immunotherapy tolerance. KRAS mutation-induced over-expression of key enzyme CD39 is believed to be involved in shaping the immunosuppressive TME, as it catalyzes the hydrolysis of extracellular ATP into immunosuppressive adenosine. Meanwhile, the loss of equilibrative nucleoside transporters (ENTs) leads to the accumulation of adenosine and the intracellular delivery difficulty of gemcit

SUBMITTER: Fan H 

PROVIDER: S-EPMC12520539 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature