title: 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 pharmacologic 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 pharmacologic therapies differ in their effect on tumor growth, proliferation, and metabolism and discuss the available preclinical and clinical evidence in favor of 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.
  
  
  
  To our knowledge, this is the first review article that comprehensively analyzes the preclinical and preliminary clinical experimental foundations of both dietary and pharmacologic metabolic interventions in cancer therapy. Among several promising therapies, we propose treatment personalization on the basis of tumor genetics, tumor metabolism, and patient systemic metabolism.Cancer Discov; 6(12); 1315-33. ©2016 AACR.
authors.affiliation: Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. claudio.vernieri@istitutotumori.mi.it valter.longo@ifom.eu.|Fondazione Istituto FIRC di Oncologia Molecolare (IFOM), Milan, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Vernieri
authors.affiliation: Fondazione Istituto FIRC di Oncologia Molecolare (IFOM), Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Casola
authors.affiliation: Fondazione Istituto FIRC di Oncologia Molecolare (IFOM), Milan, Italy.|Universita' degli Studi di Milano, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Foiani
authors.affiliation: Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Pietrantonio
authors.affiliation: Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.|Universita' degli Studi di Milano, Milan, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: de Braud
authors.affiliation: Fondazione Istituto FIRC di Oncologia Molecolare (IFOM), Milan, Italy. claudio.vernieri@istitutotumori.mi.it valter.longo@ifom.eu.|Longevity Institute, Davis School of Gerontology, University of Southern California, Los Angeles, California.
authors.forename: Valter
authors.initials: V
authors.lastname: Longo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D004035:Diet Therapy; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000187:drug effects*; D009369:Neoplasms / Q000178:diet therapy* / Q000188:drug therapy* / Q000378:metabolism; D057285:Precision Medicine
chemical_list: D000970:Antineoplastic Agents