KRAS Inhibition Activates an Actionable CD24 "Do Not Eat Me" Signal in Pancreatic Cancer.

ABSTRACT: KRASG12C inhibitors (G12Ci) have produced encouraging, albeit modest and transient, clinical benefit in pancreatic ductal adenocarcinoma (PDAC). Identifying and targeting resistance mechanisms to G12Ci treatment are therefore crucial. To better understand the function of KRASG12C and possible G12Ci bypass mechanisms, we developed an autochthonous KRASG12C-driven PDAC model. Compared with the classical KRASG12D PDAC model, the G12C model exhibits slower tumor growth, yet similar histopathologic and molecular features. Aligned with clinical experience, G12Ci treatment of KRASG12C tumors produced modest impact despite stimulating a "hot" tumor immune microenvironment. Immunoprofiling revealed that CD24, a "do not eat me" signal, is significantly upregulated on cancer cells upon G12Ci treatmen

SUBMITTER: Wei Y 

PROVIDER: S-EPMC12515478 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature