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Napabucasin, an oral drug marketed as a cancer stemness inhibitor, was tested in 1,134 people with untreated metastatic pancreatic cancer on top of nab-paclitaxel and gemcitabine; survival was identical and the trial was stopped for futility.
Napabucasin is bioactivated by NQO1 to generate reactive oxygen species and was developed as an inhibitor of STAT3-driven stemness. CanStem111P randomised 1,134 patients across 165 sites in 20 countries to napabucasin with nab-paclitaxel and gemcitabine or chemotherapy alone; median overall survival was 11.4 against 11.7 months (hazard ratio 1.07, 95 percent confidence interval 0.93 to 1.23), with no difference in the 382 patients whose tumours were positive for phosphorylated STAT3, and the trial was terminated for futility. Grade 3 or worse diarrhoea (11.6 against 4.9 percent) and abdominal pain (10.0 against 4.8 percent) were commoner with napabucasin. The trial remains the largest randomised dataset of nab-paclitaxel and gemcitabine and a reference control arm for first-line metastatic disease.
NQO1-dependent redox cycling producing reactive oxygen species; reduces STAT3 phosphorylation and stemness gene expression in preclinical models. Connects to STAT3.
1.Napabucasin slips into a pocket on STAT3.
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Query for this drug: (TITLE:"Napabucasin" OR ABSTRACT:"Napabucasin" OR TITLE:"BBI-608" OR ABSTRACT:"BBI-608" OR TITLE:"BBI608" OR ABSTRACT:"BBI608") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Napabucasin, not a curated reading list.
Shares Pancreatic cancer: the failed and stopped programmes and why, Metastatic pancreatic ductal adenocarcinoma, Pancreatic ductal adenocarcinoma.
Shares Pancreatic cancer: the failed and stopped programmes and why, Metastatic pancreatic ductal adenocarcinoma, Pancreatic ductal adenocarcinoma.
Shares Pancreatic cancer: the failed and stopped programmes and why, Metastatic pancreatic ductal adenocarcinoma, Pancreatic ductal adenocarcinoma.
Shares Pancreatic cancer: the failed and stopped programmes and why, Metastatic pancreatic ductal adenocarcinoma, Pancreatic ductal adenocarcinoma.
Shares Pancreatic cancer: the failed and stopped programmes and why, Metastatic pancreatic ductal adenocarcinoma, Pancreatic ductal adenocarcinoma.
Shares Pancreatic cancer: the failed and stopped programmes and why, Metastatic pancreatic ductal adenocarcinoma, Pancreatic ductal adenocarcinoma, Colorectal cancer.
Shares Pancreatic cancer: the failed and stopped programmes and why, Metastatic pancreatic ductal adenocarcinoma, Pancreatic ductal adenocarcinoma, Colorectal cancer.
Shares Pancreatic cancer: the failed and stopped programmes and why, Metastatic pancreatic ductal adenocarcinoma, Pancreatic ductal adenocarcinoma.