443,451 Cells Show How Pancreatic Cancer Shifts to Survive

Jeff's Daily Pick. Researchers read the genes of 443,451 single cells from pancreatic tumors. Each tumor held up to 11 competing clones, and one gene helped the worst ones win.

In the United States, researchers at NYU Langone Health and its Perlmutter Cancer Center published one of the largest single cell studies of pancreatic ductal adenocarcinoma in Nature Genetics on October 13, 2026. The disease kills nearly 85% of patients within five years of diagnosis, largely because it resists treatment and spreads.

The atlas

The team profiled 62 primary tumors from 56 patients with single cell RNA sequencing, covering 443,451 cells. For 11 tumors, spatial transcriptomics mapped gene activity at 53,236 tissue spots, and six patients gave samples before and after chemotherapy. Individual tumors contained, on average, between two and eleven genetically distinct clones, mixes of classical and basal cancer cells. Basal cells are the more aggressive type.

The MYC finding

By tracing each clone's genetic history, the researchers linked DNA copy changes to the behavior of the cells. Amplifications of genes for signaling molecules or their receptors increased the matching cell to cell interactions, while deletions suppressed them. Focal amplification of the 8q24 region, which contains the MYC oncogene, was recurrently associated with transitions from the classical to the basal state, more often than chance. In mouse and primary human models, knocking down MYC reactivated classical programs and restored immune response pathways. In the same clones, PD1 activity was suppressed, which may help explain why immunotherapies targeting PD1 rarely work in this cancer.

Study author Aristotelis Tsirigos said clinical trials of MYC and TIGIT inhibitors are underway in pancreatic and other cancers, and that the findings should push researchers to match treatments to cancer cell states rather than treating each tumor as one disease. The practical lesson is that a single biopsy captures a moment in a tumor that keeps evolving.