Bazedoxifene as a novel strategy for treatment of pancreatic and gastric adenocarcinoma

Article Article scientifique Article Bazedoxifene as a novel strategy for treatment of pancreatic and gastric adenocarcinoma eng 2019 author Burkhardt Claudia 875248 author Buehler Leo Hans 71923 author Tihy Matthieu 914217 author Morel Philippe 22337 author Forni Michel 26452 3198-3202 31139333 1949-2553 Experimental studies have shown that the IL6/GP130/STAT3 pathway is involved in pancreatic cancer tumorigenesis and progression as well as in the development of other tumors. Bazedoxifene, a selective estrogene receptor modulator clinically available for the treatment of osteoporosis, has been shown to be an effective GP130/STAT3 signaling inhibitor through in vitro and small animal studies. Our aim was to investigate the effect of bazedoxifene on tumor progression in patients with advanced pancreatic and gastric tumors. We analyzed the data of 7 patients (5 suffering from pancreatic and 2 from gastric adenocarcinoma), with locally advanced and/or metastatic disease, median age 73 years old (range 48 - 86 years). Bazedoxifene was given orally at a dose of 20 mg per day for a median duration of 9 months (range 5 - 14 months). Two patients received bazedoxifene as monotherapy, 5 patients were under concomitant chemotherapy. Results showed tumor marker reduction in 5 patients, stable disease on CT in 5 patients and metabolic regression on PET-CT in 3 patients. Weight was gained in 4 patients. Two patients developed deep vein thrombosis and one pulmonary embolism, the treatment was otherwise well tolerated. An immunhistochemical study of pSTAT3 was performed in 6 patients, out of which 3 were positive. Our preliminary data indicate that bazedoxifene is a potential new therapeutic option for pancreatic and gastric cancer therapy, safe to use and at low cost. It might be administrated at an early stage with current strategies. Based on these preliminary results, we will initiate a prospective clinical study. STAT transcription factors cytokine receptor GP130 gastric adenocarcinoma pancreatic adenocarcinoma selective estrogene receptor modulator Dewey 616.07 Dewey 617 137 Département de pathologie et immunologie 21F 57 Département de chirurgie 222 false 270 Cultures cellulaires et transplantations 519 562 Transplantation et hépatologie 905 Oncotarget 10 34 1a0b68bb-9920-497e-b45a-8b204baa106d Article (Published version) Public Article-5.pdf 2177973 application/pdf CC BY openAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté de médecine / Section de médecine clinique / Département de chirurgie

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Nouveaux isotopes pour le diagnostic et traitement du cancer du pancréas, une collaboration avec le CERN		2020	266	860
Bazedoxifene as a novel strategy for treatment of pancreatic and gastric adenocarcinoma	Oncotarget	2019	321	181

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Burkhardt, Claudia