|Cancer stem cells (CSCs): metabolic strategies for their identification and eradication|
CSC have been regarded as the cells of origin of cancer and are crucially involved in metastatic dissemination, radioresistance and chemoresistance, and disease recurrence. Mounting experimental evidence and clinical studies indicate that metabolism is not a mere player in the tumor bioenergy machinery, but it actually orchestrates stemness by enabling cell reprogramming in response to a large repertoire of environmental conditions within the stem niche. Recently, targeting the peculiar metabolic features of CSCs has hold promise to prevent disease progression and recurrence and efficiently eradicate cancer. High-throughput data combined with large-scale drug screening represent the state of the art for the characterization of the metabolic peculiarity of CSCs and the identification of selective pharmacological targets. In this scenario, the repurposing of FDA-approved drugs represents a concrete and inexpensive opportunity to extend the pharmacological and biological properties of existing compounds, and in the meanwhile gain a better understanding of CSC action in cancer. Nevertheless, a deeper focus on the metabolic plasticity of CSCs and their ability to switch to different metabolic pathways in response to certain environmental stressors like hypoxia or chemotherapics would provide a better strategic platform to hit this biochemical malleability. Furthermore, the evaluation of the metabolic fuels, intermediates, and pathways involved in maintaining the stemness traits and implicated in CSC survival in harsh conditions could unveil novel metabolic Achille's heels to be used in a therapeutic setting. A drug-controlled process aimed at forcing CSCs to adopt a certain metabolic profile could be an effective approach to prevent the metabolic adaptability of CSCs. Indeed, targeting this drug-induced metabolic inflexibility would definitely compromise CSC survival.
Biochemical Journal (2018) 475 1611–1634 doi.org