Oncologie

, Volume 15, Issue 9, pp 467–473 | Cite as

Cibler le métabolisme tumoral : efficacité et perspectives

Mise au point / Update

Résumé

La reprogrammation métabolique est une caractéristique fondamentale du cancer qui va lui permettre d’assurer la production des métabolites nécessaires à sa croissance et sa prolifération. De nombreux oncogènes entraînent une reprogrammation métabolique cellulaire; celle-ci fait partie de leur pouvoir transformant et illustre l’intérêt potentiel de cibler le métabolisme. Les antimétabolites comme le méthotrexate et l’asparaginase dans les leucémies aiguës ont apporté la preuve du concept du ciblage du métabolisme tumoral. Cela justifie le développement de nouvelles substances dans ce domaine. Les défis sont multiples: éviter la toxicité par l’inhibition des voies métaboliques des cellules normales, anticiper les voies redondantes qui pourraient limiter toute efficacité thérapeutique, identifier de nouvelles cibles et de nouveaux biomarqueurs. Le ciblage du métabolisme s’intègre donc dans une démarche de médecine personnalisée. Les voies métaboliques pour lesquelles des études, précliniques pour la plupart, sont en cours sont celles du métabolisme du glucose, de la glutamine, des acides gras et des acides aminés ainsi que la voie du cycle de Krebs. L’identification de nouvelles cibles passe par une modélisation des réseaux métaboliques cancéreux via la modélisation métabolique à l’échelle génomique (GSMM) pour laquelle la preuve du concept a été établie. Cibler le métabolisme tumoral est donc une piste thérapeutique efficace, prometteuse avec des données principalement précliniques à l’heure actuelle. Des essais cliniques sont amenés à être mis en place dans un futur proche.

Mots clés

Métabolisme Effet Warburg Cycle de Krebs Antimétabolite Thérapie ciblée 

Targeting cancer cell metabolism: evidences and perspectives

Abstract

Metabolic reprogramming is a hallmark of cancer which will provide tumor cells with all metabolites needed for growth and proliferation. Numerous oncogenes are responsible for a cellular metabolic reprogramming as part of their transforming role which illustrates the potential therapeutic advantage of targeting cancer metabolism. Anti-metabolites drugs, such as methotrexate or L-asparignase, have proven to be effective in many cancers and brought the proof of concept of cancer metabolism targeting. This justifies the development of new agents in this domain. When developing such molecules, many challenges are faced: to avoid toxicity linked to metabolism inhibition of normal cells, to anticipate redundancy of metabolic pathways which could abrogate efficacy, and to identify new targets and biomarkers. Therefore, cancer metabolism targeting is part of oncologic personalized medicine. Clinical and mostly pre-clinical researches are ongoing for glucose, glutamine, fatty acids, amino acids metabolism, and TCA cycle targeting. Genome scale Metabolic Modeling (GSMM) has been proven to be effective in identifying new metabolic targets. Cancer metabolism targeting is a promising way to treat cancer which has already proven efficacy with anti-metabolite drugs. At the moment, most of the data are preclinical but clinical trial of such agents will undoubtedly be set in the future.

Keywords

TCA cycle Metabolism Warburg effect Targeted therapy Anti-metabolites 

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Copyright information

© Springer-Verlag France 2013

Authors and Affiliations

  1. 1.Inserm U935 « Modèles de cellules souches malignes et thérapeutiques » Campus CNRSVillejuifFrance
  2. 2.Département de médecineGustave-RoussyVillejuifFrance

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