Fasting Cycles Retard Growth of Tumors and Sensitize a Range of Cancer Cell Types to Chemotherapy

By Changhan Lee, L. Raffaghello, Sebastian Brandhorst, F. Safdie, G. Bianchi, A. Martín-Montalvo, Vito Pistoia, Min Wei, Saewon Hwang, A. Merlino and 3 more. Science Translational Medicine, 2012

638 citations recorded by the source corpus.

Short-term starvation increases the effectiveness of chemotherapy against a wide range of tumor cell types. Fasting: Good for You, Bad for Tumors Many promising cancer drugs being developed will require years to become approved by regulatory bodies and, in most cases, will only be effective for a fraction of patients with specific types of cancer. It is therefore important to develop broader, complementary strategies that can be translated rapidly into effective therapies. Two to 4 days of fasting before chemotherapy treatment is safe and protect animals, and possibly humans, against the side effects of chemotherapy. Here, cycles of fasting for 2 days in the absence of other treatments are shown to delay the progression of several tumor types in mice and, in some cases, to be as effective as toxic chemotherapy drugs. However, the combination of fasting and chemotherapy was much more effective than either alone and delayed the progression of a variety of tumors, including breast cancer and glioma, reduced the number of organs affected by melanoma metastases, and promoted long-term cancer-free survival in up to 40% of mice with neuroblastomas. In mice injected with human breast and ovarian cancer cells, fasting cycles promoted survival extension by protecting the mice from chemotherapy while causing a strong inhibition of tumor progression. Experiments in simple organisms, human cells, and mice indicated that these effects of fasting were caused by changes inside and outside cells that increased the death of tumor but not normal cells, a process termed differential stress sensitization. Although clinical trials testing the effect of fasting in cancer treatment are still in the early stages, they suggest that fasting cycles may boost the efficacy of chemotherapeutic agents and could be as effective as chemotherapy drugs in the killing of specific tumor cells. Short-term starvation (or fasting) protects normal cells, mice, and potentially humans from the harmful side effects of a variety of chemotherapy drugs. Here, we show that treatment with starvation conditions sensitized yeast cells (Saccharomyces cerevisiae) expressing the oncogene-like RAS2val19 to oxidative stress and 15 of 17 mammalian cancer cell lines to chemotherapeutic agents. Cycles of starvation were as effective as chemotherapeutic agents in delaying progression of different tumors and increased the effectiveness of these drugs against melanoma, glioma, and breast cancer cells. In mouse models of neuroblastoma, fasting cycles plus chemotherapy drugs—but not either treatment alone—resulted in long-term cancer-free survival. In 4T1 breast cancer cells, short-term starvation resulted in increased phosphorylation of the stress-sensitizing Akt and S6 kinases, increased oxidative stress, caspase-3 cleavage, DNA damage, and apoptosis. These studies suggest that multiple cycles of fasting promote differential stress sensitization in a wide range of tumors and could potentially replace or augment the efficacy of certain chemotherapy drugs in the treatment of various cancers.

Subfields: Aging, Endocrine and Autonomic Systems, Modeling and Simulation

View Paper: https://www.semanticscholar.org/paper/7f186769a0887bbb2bc2aad4dc99d1b5c28b3d2c

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Aging

1. Mark P. Mattson
2. Brian K. Kennedy
3. V. Longo
4. Guido Kroemer
5. P. Cohen

In Endocrine and Autonomic Systems

1. Mark P. Mattson
2. Guido Kroemer
3. M. Harvie
4. Brian K. Kennedy
5. V. Longo

Citations in the corpus

• A periodic diet that mimics fasting promotes multi-system regeneration, enhanced cognitive performance and healthspan (2015, background): “Similarly to previously reported data, we observed an age-dependent decline in BrdU incorporation in the dentate gyrus (Lee et al., 2012c) (Figure 4B).”
• Spermidine in health and disease (2018, background): “Thus, the administration of spermidine or hydroxycitrate, similar to that of acute nutrient deprivation (106), can favor chemotherapeutic efficiency against autophagy-competent cancers.”
• Impact of intermittent fasting on health and disease processes (2016, positive): “…the progression of a wide range of cancers but, more importantly, can protect normal cells from the toxic effects of chemotherapy drugs while sensitizing cancer cells to the treatment (Raffaghello et al., 2008; Lee et al., 2012; Safdie et al., 2009; Dorff et al., 2016; Lee and Longo, 2011).”
• Gut microbiota modulation of chemotherapy efficacy and toxicity (2017, positive): “Nutritional modulation of cancer metabolism is also an emerging therapeutic approach, with fasting 68,69 , carbohydrate restriction 70 , amino acid restriction (L-asparaginase 71 , methionine 72 , serine 73 , tyrosine and phenylalanine 74 ) and ketogenic diets 75 under investigation.”