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      Effects of short-term fasting on cancer treatment

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          Abstract

          Growing preclinical evidence shows that short-term fasting (STF) protects from toxicity while enhancing the efficacy of a variety of chemotherapeutic agents in the treatment of various tumour types. STF reinforces stress resistance of healthy cells, while tumor cells become even more sensitive to toxins, perhaps through shortage of nutrients to satisfy their needs in the context of high proliferation rates and/or loss of flexibility to respond to extreme circumstances. In humans, STF may be a feasible approach to enhance the efficacy and tolerability of chemotherapy. Clinical research evaluating the potential of STF is in its infancy. This review focuses on the molecular background, current knowledge and clinical trials evaluating the effects of STF in cancer treatment. Preliminary data show that STF is safe, but challenging in cancer patients receiving chemotherapy. Ongoing clinical trials need to unravel if STF can also diminish toxicity and increase efficacy of chemotherapeutic regimes in daily practice.

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          Most cited references141

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          Hallmarks of Cancer: The Next Generation

          The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer. Copyright © 2011 Elsevier Inc. All rights reserved.
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            Understanding the Warburg effect: the metabolic requirements of cell proliferation.

            In contrast to normal differentiated cells, which rely primarily on mitochondrial oxidative phosphorylation to generate the energy needed for cellular processes, most cancer cells instead rely on aerobic glycolysis, a phenomenon termed "the Warburg effect." Aerobic glycolysis is an inefficient way to generate adenosine 5'-triphosphate (ATP), however, and the advantage it confers to cancer cells has been unclear. Here we propose that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass (e.g., nucleotides, amino acids, and lipids) needed to produce a new cell. Supporting this idea are recent studies showing that (i) several signaling pathways implicated in cell proliferation also regulate metabolic pathways that incorporate nutrients into biomass; and that (ii) certain cancer-associated mutations enable cancer cells to acquire and metabolize nutrients in a manner conducive to proliferation rather than efficient ATP production. A better understanding of the mechanistic links between cellular metabolism and growth control may ultimately lead to better treatments for human cancer.
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              Obesity is associated with macrophage accumulation in adipose tissue

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                Author and article information

                Contributors
                S.de_Groot2@lumc.nl
                H.Pijl@lumc.nl
                koos.vanderhoeven@radboudumc.nl
                +31715263464 , J.R.Kroep@lumc.nl
                Journal
                J Exp Clin Cancer Res
                J. Exp. Clin. Cancer Res
                Journal of Experimental & Clinical Cancer Research : CR
                BioMed Central (London )
                0392-9078
                1756-9966
                22 May 2019
                22 May 2019
                2019
                : 38
                : 209
                Affiliations
                [1 ]ISNI 0000000089452978, GRID grid.10419.3d, Department of Medical Oncology, , Leiden University Medical Center, ; Albinusdreef 2, P.O. Box 9600, 2300RC Leiden, The Netherlands
                [2 ]ISNI 0000000089452978, GRID grid.10419.3d, Department of Endocrinology, , Leiden University Medical Center, ; P.O. Box 9600, 2300RC, Leiden, The Netherlands
                Article
                1189
                10.1186/s13046-019-1189-9
                6530042
                31113478
                f1152a3b-f5c7-4c74-8274-f254c1f53ef1
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 23 January 2019
                : 22 April 2019
                Funding
                Funded by: Pink Ribbon
                Award ID: 2012.WO31.C155
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2019

                Oncology & Radiotherapy
                short-term fasting,fasting-mimicking diet,chemotherapy,differential stress resistance,differential stress sensitization,toxicity

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