Metabolic targeting of malignant tumors: a need for systemic approach

Purpose Dysregulated metabolism is now recognized as a fundamental hallmark of carcinogenesis inducing aggressive features and additional hallmarks. In this review, well-established metabolic changes displayed by tumors are highlighted in a comprehensive manner and corresponding therapeutical targets are discussed to set up a framework for integrating basic research findings with clinical translation in oncology setting. Methods Recent manuscripts of high research impact and relevant to the field from PubMed (2000-2021) have been reviewed for this article. Results Metabolic pathway disruption during tumor evolution is a dynamic process potentiating cell survival, dormancy, proliferation and invasion even under dismal conditions. Apart from cancer cells, though, tumor microenvironment has an acting role as extracellular metabolites, pH alterations and stromal cells reciprocally interact with malignant cells, ultimately dictating tumor-promoting responses, disabling anti-tumor immunity and promoting resistance to treatments. Conclusion In the field of cancer metabolism, there are several emerging prognostic and therapeutic targets either in the form of gene expression, enzyme activity or metabolites which could be exploited for clinical purposes; both standard-of-care and novel treatments may be evaluated in the context of metabolism rewiring and indeed, synergistic effects between metabolism-targeting and other therapies would be an attractive perspective for further research.

Automated summary

Dysregulated metabolism is a fundamental characteristic of carcinogenesis, leading to aggressive features and additional hallmarks. This review provides a comprehensive overview of well-established metabolic changes in tumors and discusses potential therapeutic targets, bridging the gap between basic research and clinical application in oncology. The tumor microenvironment plays a significant role, as extracellular metabolites, pH alterations, and stromal cells interact with malignant cells, influencing tumor-promoting responses, disabling anti-tumor immunity, and promoting treatment resistance.