Cargando…
Metabolomic evaluation of Mitomycin C and rapamycin in a personalized treatment of pancreatic cancer
In a personalized treatment designed for a patient with pancreatic cancer resistant to other treatments, the success of Mitomycin C (MMC) has been highlighted. This was revealed in a murine xenograft tumor model encompassing pancreatic adenocarcinoma cells extracted from the patient. The patient was...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4186447/ https://www.ncbi.nlm.nih.gov/pubmed/25505613 http://dx.doi.org/10.1002/prp2.67 |
_version_ | 1782338063108669440 |
---|---|
author | Navarrete, Alicia Armitage, Emily G Musteanu, Monica García, Antonia Mastrangelo, Annalaura Bujak, Renata López-Casas, Pedro P Hidalgo, Manuel Barbas, Coral |
author_facet | Navarrete, Alicia Armitage, Emily G Musteanu, Monica García, Antonia Mastrangelo, Annalaura Bujak, Renata López-Casas, Pedro P Hidalgo, Manuel Barbas, Coral |
author_sort | Navarrete, Alicia |
collection | PubMed |
description | In a personalized treatment designed for a patient with pancreatic cancer resistant to other treatments, the success of Mitomycin C (MMC) has been highlighted. This was revealed in a murine xenograft tumor model encompassing pancreatic adenocarcinoma cells extracted from the patient. The patient was found to exhibit a biallelic inactivation of the PALB2 gene, involved in DNA repair in addition to another mutation in the TSC2 gene that induces susceptibility of the tumor to therapeutic targets of the PI3K-mTOR pathway. The aim of the study was to apply metabolomics to elucidate the modes of action of each therapy, suggesting why MMC was so successful in this patient and why it could be a more popular choice in future pancreatic cancer treatment. The effectiveness of MMC compared to rapamycin (RM), another relevant therapeutic agent has been evaluated through liquid- and gas-chromatography mass spectrometry-based metabolomic analyses of the xenograft tumors. The relative concentrations of many metabolites in the xenograft tumors were found to be increased by MMC relative to other treatments (RM and a combination of both), including a number that are involved in central carbon metabolism (CCM). Metabolic fingerprinting revealed statistically significantly altered pathways including, but not restricted to, the pentose phosphate pathway, glycolysis, TCA cycle, purine metabolism, fatty acid biosynthesis, in addition to many significant lipid and amino acid alterations. Given the genetic background of the patient, it was expected that the combined therapy would be most effective; however, the most effective was MMC alone. It is proposed that the effectiveness of MMC is owed to its direct effect on CCM, a vital region of tumor metabolism. |
format | Online Article Text |
id | pubmed-4186447 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-41864472014-12-03 Metabolomic evaluation of Mitomycin C and rapamycin in a personalized treatment of pancreatic cancer Navarrete, Alicia Armitage, Emily G Musteanu, Monica García, Antonia Mastrangelo, Annalaura Bujak, Renata López-Casas, Pedro P Hidalgo, Manuel Barbas, Coral Pharmacol Res Perspect Original Articles In a personalized treatment designed for a patient with pancreatic cancer resistant to other treatments, the success of Mitomycin C (MMC) has been highlighted. This was revealed in a murine xenograft tumor model encompassing pancreatic adenocarcinoma cells extracted from the patient. The patient was found to exhibit a biallelic inactivation of the PALB2 gene, involved in DNA repair in addition to another mutation in the TSC2 gene that induces susceptibility of the tumor to therapeutic targets of the PI3K-mTOR pathway. The aim of the study was to apply metabolomics to elucidate the modes of action of each therapy, suggesting why MMC was so successful in this patient and why it could be a more popular choice in future pancreatic cancer treatment. The effectiveness of MMC compared to rapamycin (RM), another relevant therapeutic agent has been evaluated through liquid- and gas-chromatography mass spectrometry-based metabolomic analyses of the xenograft tumors. The relative concentrations of many metabolites in the xenograft tumors were found to be increased by MMC relative to other treatments (RM and a combination of both), including a number that are involved in central carbon metabolism (CCM). Metabolic fingerprinting revealed statistically significantly altered pathways including, but not restricted to, the pentose phosphate pathway, glycolysis, TCA cycle, purine metabolism, fatty acid biosynthesis, in addition to many significant lipid and amino acid alterations. Given the genetic background of the patient, it was expected that the combined therapy would be most effective; however, the most effective was MMC alone. It is proposed that the effectiveness of MMC is owed to its direct effect on CCM, a vital region of tumor metabolism. Blackwell Publishing Ltd 2014-12 2014-08-24 /pmc/articles/PMC4186447/ /pubmed/25505613 http://dx.doi.org/10.1002/prp2.67 Text en © 2014 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Navarrete, Alicia Armitage, Emily G Musteanu, Monica García, Antonia Mastrangelo, Annalaura Bujak, Renata López-Casas, Pedro P Hidalgo, Manuel Barbas, Coral Metabolomic evaluation of Mitomycin C and rapamycin in a personalized treatment of pancreatic cancer |
title | Metabolomic evaluation of Mitomycin C and rapamycin in a personalized treatment of pancreatic cancer |
title_full | Metabolomic evaluation of Mitomycin C and rapamycin in a personalized treatment of pancreatic cancer |
title_fullStr | Metabolomic evaluation of Mitomycin C and rapamycin in a personalized treatment of pancreatic cancer |
title_full_unstemmed | Metabolomic evaluation of Mitomycin C and rapamycin in a personalized treatment of pancreatic cancer |
title_short | Metabolomic evaluation of Mitomycin C and rapamycin in a personalized treatment of pancreatic cancer |
title_sort | metabolomic evaluation of mitomycin c and rapamycin in a personalized treatment of pancreatic cancer |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4186447/ https://www.ncbi.nlm.nih.gov/pubmed/25505613 http://dx.doi.org/10.1002/prp2.67 |
work_keys_str_mv | AT navarretealicia metabolomicevaluationofmitomycincandrapamycininapersonalizedtreatmentofpancreaticcancer AT armitageemilyg metabolomicevaluationofmitomycincandrapamycininapersonalizedtreatmentofpancreaticcancer AT musteanumonica metabolomicevaluationofmitomycincandrapamycininapersonalizedtreatmentofpancreaticcancer AT garciaantonia metabolomicevaluationofmitomycincandrapamycininapersonalizedtreatmentofpancreaticcancer AT mastrangeloannalaura metabolomicevaluationofmitomycincandrapamycininapersonalizedtreatmentofpancreaticcancer AT bujakrenata metabolomicevaluationofmitomycincandrapamycininapersonalizedtreatmentofpancreaticcancer AT lopezcasaspedrop metabolomicevaluationofmitomycincandrapamycininapersonalizedtreatmentofpancreaticcancer AT hidalgomanuel metabolomicevaluationofmitomycincandrapamycininapersonalizedtreatmentofpancreaticcancer AT barbascoral metabolomicevaluationofmitomycincandrapamycininapersonalizedtreatmentofpancreaticcancer |