Metabolic modification in gastrointestinal cancer stem cells: characteristics and therapeutic approaches

Currently, there is much interest in the characterization of metabolic profiling of cancer stem cells (CSCs), a small subset of tumor cells with self-renewal capacity. Indeed, ever-growing evidence indicate that metabolism and stemness are highly intertwined processes in tumor tissue. In this review, we analyze the potential metabolic targeting strategies for eradicating CSCs that could help to develop a more effective therapeutic approach for gastrointestinal cancers. Indeed, the successful elimination of a tumor requires an anticancer therapy that affects both cancer cells and CSCs. The observation that gastrointestinal CSCs possess higher inducible nitric oxide sinthase (iNOS) expression, lower reactive oxygen species (ROS) production, and a different metabolism respect to no-CSCs tumor cells has paved the way to develop drugs targeting CSC specific signaling. In particular, several studies have highlighted that metformin, aldehyde dehydrogenase 1, and iNOS inhibitors selectively suppressed CSC growth and that combinatorial therapy of them with standard chemotherapeutic drugs had a synergistic effect resulting in reduced tumor burden and delayed tumor recurrence. Thus, the possibility of combining specific CSC metabolism inhibitors with existing therapeutic approaches could have profound anticancer effects, changing the conventional treatment approaches to gastrointestinal cancers