Use of metabolic pathway flux information in targeted cancer drug design
Knowledge of tumor-specific metabolic pathway flux, obtainable via the emerging tool of stable isotope-based dynamic metabolic profiling (SIDMAP), identifies metabolic enzyme drug targets which might help to overcome difficulties related to resistance to currently evolving targeted therapies against more narrowly conceived gene or protein targets. An accurate metabolic map detailing metabolic pathway substrate flow (flux) of the many tumor cell phenotypes is essential to design effective targeted cancer drugs and to accurately predict drug response. Lance Liotta – National Institutes of Health, Bethesda, MD, USA Neil Gibson – OSI Pharmaceuticals, NY, USA The high rate of metabolism of certain cancers affords an opportunity to understand better the pathways on which cancer cells might be dependent. Here, László Boros et al. review how metabolic profiling (e.g. glucose use and fatty acid synthesis) can clarify the mechanisms by which certain tumors develop resistance to molecular targeted therapies (MTTs). Ultimately, the use of such information could lead to the identification of new therapies that, when used in combination with MTTs, might offer new options in the treatment of cancer.