Targeting Cancer Metabolism: Dietary and Pharmacologic Interventions

Abstract

Most tumors display oncogene-driven reprogramming of several metabolic pathways, which are crucial to sustain their growth and proliferation. In recent years, both dietary and pharmacological approaches that target deregulated tumor metabolism are beginning to be considered for clinical applications. Dietary interventions exploit the ability of nutrient-restricted conditions to exert broad biological effects, protecting normal cells, organs and systems, while sensitizing a wide variety of cancer cells to cytotoxic therapies. On the other hand, drugs targeting enzymes or metabolites of crucial metabolic pathways can be highly specific and effective, but must be matched with a responsive tumor, which might rapidly adapt. In this Review, we illustrate how dietary and pharmacological therapies differ in their effect on tumor growth, proliferation and metabolism, and discuss the available preclinical and clinical evidence in favor or against each of them. We also indicate, when appropriate, how to optimize future investigations on metabolic therapies on the basis of tumor- and patient-related characteristics.

Impact of systemic and tumor lipid metabolism on everolimus efficacy in advanced pancreatic neuroendocrine tumors (pNETs)

“…In pNETs, mutations of ACC1 and FASN genes have not been reported . Therefore, the corresponding pathways are more likely to be regulated through modifications of enzyme expression or post‐translational modifications, as described in other neoplasms . Our data showing coherent intratumor expression of ACC1 and FASN at both protein and mRNA level suggest that these enzymes are coregulated in pNET cells.…”

“…Lipids are another class of metabolites that crucially contribute to cell bioenergetics and anabolic functions . Differently from normal tissues, most human cancers synthesize fatty acids de novo from acetyl‐CoA units .…”

Beyond Computational Genomics towards Systems Metabolomics for Precision Oncology

“…In this note I am focusing on new properties linked to metabolism, which is a the crossroad of growth and death of cancer cells. In this context one has also to put attention to the possibility that diet may interfere with drug treatment (75).…”

Redefining advances in modern oncology research

“…Two emerging hallmarks of cancer -reprogramming of energy metabolism and evading immune destruction -have been recognized as additional biological capabilities acquired during the progression of human tumors [1] . Now, we have a better understanding of the fundamentals of cancer metabolism [2] and various approaches targeting cancer metabolism for clinical applications are emerging [3] . The Cancer Genome Atlas…”