Overview
- The study, published Tuesday online in Nature Genetics, profiled 443,451 single cells from 62 pancreatic tumors to trace how distinct clones change over time.
- Researchers found multiple genetically distinct clones coexisting in the same tumor that follow different paths, with some clones acquiring therapy resistance and others gaining metastatic traits.
- MYC activity was higher in aggressive basal clones and laboratory MYC blockade shifted those cells toward the less aggressive classical state while increasing immune exposure.
- Some clones showed increased TIGIT expression together with suppressed PD‑1 activity, a pattern that may help explain why PD‑1–targeting immunotherapies rarely work in pancreatic ductal adenocarcinoma.
- Investigators say the results support using single-cell profiling for better biomarkers, urge larger clinical studies, and note that trials of MYC and TIGIT inhibitors are underway but not yet conclusive for patients.