CEND-1: a game changer for pancreatic cancer chemotherapy?

Abstract

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. 1 Springfeld C Jäger D Büchler MW et al. Chemotherapy for pancreatic cancer. Presse Med. 2019; 48: e159-e174 Crossref PubMed Scopus (83) Google Scholar 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. 2 Hosein AN Brekken RA Maitra A Pancreatic cancer stroma: an update on therapeutic targeting strategies. Nat Rev Gastroenterol Hepatol. 2020; 17: 487-505 Crossref PubMed Scopus (228) Google Scholar 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 3 Dean A Gill S McGregor M Broadbridge V Järveläinen HA Price T Dual αV-integrin and neuropilin-1 targeting peptide CEND-1 plus nab-paclitaxel and gemcitabine for the treatment of metastatic pancreatic ductal adenocarcinoma: a first-in-human, open-label, multicentre, phase 1 study. Lancet Gastroenterol Hepatol. 2022; (published online July 5.)https://doi.org/10.1016/S2468-1253(22)00167-4 Summary Full Text Full Text PDF PubMed Google Scholar 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. Dual αV-integrin and neuropilin-1 targeting peptide CEND-1 plus nab-paclitaxel and gemcitabine for the treatment of metastatic pancreatic ductal adenocarcinoma: a first-in-human, open-label, multicentre, phase 1 studyCEND-1 with nab-paclitaxel and gemcitabine has an acceptable safety profile, with no dose-limiting toxicities and encouraging activity. Adverse events were generally consistent with those seen with nab-paclitaxel and gemcitabine. Further randomised trials to determine the efficacy of CEND-1 are warranted. Full-Text PDF