Cibler le métabolisme tumoral: efficacité et perspectives

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.