Cancer stem cells (CSCs) are a highly tumorigenic population of pancreatic ductal adenocarcinoma (PDAC) cells that contribute to tumor progression, metastasis, therapy resistance and disease relapse. In this study, Pérez-Ruiz and colleagues investigated apMNKQ2, a DNA aptamer targeting MNK1, a protein involved in PDAC progression and CSC maintenance. Using patient-derived models, the authors showed that apMNKQ2 impaired pancreatic cancer cell growth and several properties associated with tumor aggressiveness. Importantly, the aptamer strongly affected the CSC population, markedly reducing its ability to self-renew and initiate new tumors. The study also demonstrated that apMNKQ2 can reach tumors following systemic administration and showed a favorable safety profile in preclinical models. Together, these findings identify MNK1 as a promising therapeutic vulnerability in pancreatic CSCs and support the further development of apMNKQ2 as a potential new therapeutic strategy for PDAC.

The study was led by Bruno Sainz from the Instituto de Investigaciones Biomédicas, Madrid, and published in the Journal of Biomedical Sciences.

PMID 42410607

doi: 10.1186/s12929-026-01275-6