Abstract
Evaluation of efficacy of oral administration of pro-drug of triptolide against pancreatic cancer
Journal of clinical oncology, Vol.35(4_suppl), pp.296-296
02/01/2017
DOI: 10.1200/JCO.2017.35.4_suppl.296
Abstract
Abstract only 296 Background: Pancreatic cancer is an aggressive disease. The current chemotherapy only marginally increases the survival of patients with PDAC. Hence there is an urgent need for novel therapies. We have shown that minnelide, a pro-drug of triptolide which is currently in phase I trials, when administered intra-peritoneally is very effective against pancreatic cancer in multiple animal models. In the current study we evaluated the efficacy of oral minnelide against pancreatic cancer, alone or in combination with standard therapy in PDAC. Methods: Xenograft, subcutaneous and orthotopic models were established using S2-VP10 and MIA PaCa-2 cell lines. Minnelide was used in doses ranging from 0.15-0.6 mg/kg/day either oral or i.p. and standard chemotherapy was gemcitabine 250 mg/kg/week + nab-paclitaxel 25 mg/kg/week. The tumor burden was compared between various treatment groups. Results: Minnelide i.p significantly decreased tumor mass in MIA PaCa-2 derived tumors and oral administration had equipotent effects. In the S2-VP10 model, combination of low doses of orally administered minnelide with gemcitabine + nab-paclitaxel was significantly more effective in decreasing the tumor burden leading to an increased survival of tumor bearing mice when compared with either therapy alone (p < 0.05). Combination therapy significantly reduced cancer-related morbidity by decreasing ascites and metastasis. Conclusions: Oral administration of minnelide is effective against pancreatic cancer at doses which have been shown to be safe in phase I clinical trial. Oral minnelide has great potential to emerge as novel therapy for pancreatic cancer.
Details
- Title: Subtitle
- Evaluation of efficacy of oral administration of pro-drug of triptolide against pancreatic cancer
- Creators
- Vikas Dudeja - Vikas Dudeja, Miami, FLNikita Sharma - University of MiamiShrey Modi - University of MiamiNipun B. Merchant - Vanderbilt-Ingram Cancer CenterSelwyn M. Vickers - University of Alabama at BirminghamSulagna Banerjee - University of MiamiAshok Saluja - University of Miami
- Resource Type
- Abstract
- Publication Details
- Journal of clinical oncology, Vol.35(4_suppl), pp.296-296
- DOI
- 10.1200/JCO.2017.35.4_suppl.296
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Publisher
- AMER SOC CLINICAL ONCOLOGY
- Language
- English
- Date published
- 02/01/2017
- Academic Unit
- Anatomy and Cell Biology; Surgery
- Record Identifier
- 9985244566902771
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