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MEK inhibitors cobimetinib and trametinib, regressed a gemcitabine-resistant pancreatic-cancer patient-derived orthotopic xenograft (PDOX).
- Source :
-
Oncotarget [Oncotarget] 2017 Jul 18; Vol. 8 (29), pp. 47490-47496. - Publication Year :
- 2017
-
Abstract
- A pancreatic ductal adenocarcinoma (PDAC), obtained from a patient, was grown orthotopically in the pancreatic tail of nude mice to establish a patient-derived orthotopic (PDOX) model. Seven weeks after implantation, PDOX nude mice were divided into the following groups: untreated control (n = 7); gemcitabine (100 mg/kg, i.p., once a week for 2 weeks, n = 7); cobimetinib (5 mg/kg, p.o., 14 consecutive days, n = 7); trametinib (0.3 mg/kg, p.o., 14 consecutive days, n = 7); trabectedin (0.15 mg/kg, i.v., once a week for 2 weeks, n = 7); temozolomide (25 mg/kg, p.o., 14 consecutive days, n = 7); carfilzomib (2 mg/kg, i.v., twice a week for 2 weeks, n = 7); bortezomib (1 mg/kg, i.v., twice a week for 2 weeks, n = 7); MK-1775 (20 mg/kg, p.o., 14 consecutive days, n = 7); BEZ-235 (45 mg/kg, p.o., 14 consecutive days, n = 7); vorinostat (50 mg/kg, i.p., 14 consecutive days, n = 7). Only the MEK inhibitors, cobimetinib and trametinib, regressed tumor growth, and they were more significantly effective than other therapies (p < 0.0001, respectively), thereby demonstrating the precision of the PDOX models of PDAC and its potential for individualizing pancreatic-cancer therapy.
- Subjects :
- Animals
Cell Line, Tumor
Deoxycytidine analogs & derivatives
Deoxycytidine pharmacology
Disease Models, Animal
Dose-Response Relationship, Drug
Humans
Mice
Pancreatic Neoplasms diagnostic imaging
Pancreatic Neoplasms drug therapy
Pancreatic Neoplasms metabolism
Pancreatic Neoplasms pathology
Xenograft Model Antitumor Assays
Gemcitabine
Antineoplastic Agents pharmacology
Azetidines pharmacology
Drug Resistance, Neoplasm drug effects
Mitogen-Activated Protein Kinases antagonists & inhibitors
Piperidines pharmacology
Protein Kinase Inhibitors pharmacology
Pyridones pharmacology
Pyrimidinones pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 8
- Issue :
- 29
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 28537897
- Full Text :
- https://doi.org/10.18632/oncotarget.17667