The laboratory of Dr. Jason Locasale focuses on an integrated understanding of the role of altered metabolism in cancer. Successful therapeutic strategies to exploit these altered metabolic states have begun to show some promise but the biomarkers that guide these interventions are still poorly understood. Dr. Locasale’s lab is developing quantitative models of glucose metabolism to derive predictors of therapeutic agents that target cancer metabolism.
The current issue of Cell Metabolism features an article by the Locasale team discussing their work on determining the mechanism for how the diabetes drug metformin can be used to treat ovarian cancer. Using patient samples (including those from a ‘‘superresponder’’), animal tumors, and cell culture experiments, they find that the predominant mechanism of action by metformin in cancer is to target tumor cell-intrinsic mitochondrial metabolism.
By integrating data from metabolic features remnant in human patient tumors with idealized responses in pre-clinical models, the team was able to provide insight into the nature of metformin’s effect on cancer and identify new aspects of metabolism that are controlled by mitochondria. With this deeper biochemical and systems-level understanding using a thorough metabolomics platform, they identified many of the pleiotropic features that determine an anti-cancer response to metformin. Hopefully these results will inform the design and patient selection for upcoming clinical investigations.