The clinical development of systemic therapies for patients with metastatic pancreatic ductal adenocarcinoma has been a series of disappointments. Immunotherapy has been largely ineffective, targeted therapy only works in a few patients, and chemotherapy is less effective than in other cancer types. There are more than 530 000 deaths worldwide each year, ranking pancreatic ductal adenocarcinoma as the fifth most common cause of cancer death. In the USA there has been a small improvement in 5-year survival for all stages, increasing from approximately 5% to 11% in the past three decades, but this increase is insignificant when compared with other tumour types. Pancreatic ductal adenocarcinoma is characterised by a dense desmoplastic stroma that might contribute to chemotherapy resistance. Cancer-associated fibroblasts secrete TGF-β which promotes the stromal matrix and αvβ5 integrin expression involved in cancer cell adhesion, migration, and proliferation. In The Lancet Gastroenterology & Hepatology, Andrew Dean and colleagues report the results from a phase 1 study in patients with untreated metastatic pancreatic ductal adenocarcinoma that might be a game changer at enhancing tumour delivery of standard chemotherapy by coadministration with the CEND-1 cyclic peptide.