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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.

SUBMITTER: Vernieri C

PROVIDER: S-EPMC5140697 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Targeting Cancer Metabolism: Dietary and Pharmacologic Interventions.

Vernieri Claudio C Casola Stefano S Foiani Marco M Pietrantonio Filippo F de Braud Filippo F Longo Valter V

Cancer discovery 20161121 12

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 ...[more]

PMID: 27872127

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Project description:ImportanceImproved survival in patients with advanced cancer has increased the need for better understanding of how to manage common symptoms that they may experience, such as breathlessness.ObjectiveTo assess the benefits and harms associated with pharmacologic interventions for breathlessness in adults with advanced cancer.Data sourcesPubMed, Embase, CINAHL, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for studies published from database inception through May 31, 2020, using predefined eligibility criteria within a PICOTS (population, intervention, comparator, outcome, timing, setting) format.Study selectionRandomized clinical trials (RCTs), non-RCTs, and observational studies with a comparison group that evaluated benefits and/or harms and cohort studies that reported harms were selected.Data extraction and synthesisTwo reviewers independently screened studies for eligibility, serially abstracted data, independently assessed risk of bias, and graded strength of evidence (SOE).Main outcomes and measuresBenefits and harms of pharmacologic interventions were compared, focusing on breathlessness, anxiety, exercise capacity, and health-related quality of life. When possible, meta-analyses were conducted and standardized mean differences (SMDs) calculated.ResultsIn this systematic review and meta-analysis, a total of 7729 unique citations were identified, of which 19 studies (17 RCTs and 2 retrospective studies) that included a total of 1424 patients assessed the benefits of medications for management of breathlessness in advanced cancer or reported harms. The most commonly reported type of cancer was lung cancer. Opioids were not associated with more effectiveness than placebo for improving breathlessness (SMD, -0.14; 95% CI, -0.47 to 0.18) or exercise capacity ( SMD, 0.06; 95% CI, -0.43 to 0.55) (SOE, moderate); most studies examined exertional breathlessness. Specific dose and/or route of administration of opioids did not differ in effectiveness for breathlessness (SMD, 0.15; 95% CI, -0.22 to 0.52) (SOE, low). Anxiolytics were not associated with more effectiveness than placebo for breathlessness or anxiety (reported mean between-group difference, -0.52; 95% CI, -1.045 to 0.005) (SOE, low). Evidence for other pharmacologic interventions was limited. Pharmacologic interventions demonstrated some harms compared with usual care, but dropout attributable to adverse events was minimal in these short-term studies (range 3.2%-16%).Conclusions and relevanceEvidence did not support the association of opioids or other pharmacologic interventions with improved breathlessness. Given that studies had many limitations, pharmacologic interventions should be considered in selected patients but need to be considered in the context of potential harms and evidence of an association of nonpharmacologic interventions with improved breathlessness.

Dataset Information

Targeting Cancer Metabolism: Dietary and Pharmacologic Interventions.

Publications

Targeting Cancer Metabolism: Dietary and Pharmacologic Interventions.

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