Fasting to enhance Cancer treatment in models: the next steps

Abstract

Short-term fasting (STF) is a technique to reduce nutrient intake for a specific period. Since metabolism plays a pivotal role in tumor progression, it can be hypothesized that STF can improve the efficacy of chemotherapy. Recent studies have demonstrated the efficacy of STF in cell and animal tumor models. However, large-scale clinical trials must be conducted to verify the safety and effectiveness of these diets. In this review, we reexamine the concept of how metabolism affects pathophysiological pathways. Next, we provided a comprehensive discussion of the specific mechanisms of STF on tumor progression, derived through studies carried out with tumor models. There are currently at least four active clinical trials on fasting and cancer treatment. Based on these studies, we highlight the potential caveats of fasting in clinical applications, including the onset of metabolic syndrome and other metabolic complications during chemotherapy, with a particular focus on the regulation of the epithelial to mesenchymal pathway and cancer heterogeneity. We further discuss the advantages and disadvantages of the current state-of-art tumor models for assessing the impact of STF on cancer treatment. Finally, we explored upcoming fasting strategies that could complement existing chemotherapy and immunotherapy strategies to enable personalized medicine. Overall, these studies have the potential for breakthroughs in cancer management.

Starvation and Climate Change—How to Constrain Cancer Cell Epigenetic Diversity and Adaptability to Enhance Treatment Efficacy

“…The benefits of fasting for cancer and other diseases have been carefully reviewed elsewhere (Nencioni et al, 2018;de Cabo and Mattson, 2019;Caffa et al, 2020;Tajan and Vousden, 2020;Zhang J. et al, 2020). Pre-clinical (Lee et al, 2012;Brandhorst et al, 2015;Wei et al, 2017;de Cabo and Mattson, 2019;Caffa et al, 2020), and early clinical studies (Caffa et al, 2020;de Groot et al, 2020), show benefits for coupling fasting or fasting-mimicking diets (FMDs) with chemotherapy and/or endocrine therapy, including enhanced treatment efficacy, reduce side effects and the prevention of drug resistance.…”

Obesity and Cancer Metastasis: Molecular and Translational Perspectives

“…Another proposed method to target the metabolism of tumor cells is through short term dietary fasting. Fasting diets are currently in clinical trial to enhance chemotherapy efficacy and reduce toxicity however there is also evidence they may slow tumor progression [235]. In the fasting state IGF-1, a promoter of EMT, is inhibited, and clinical trials are underway to investigate if tumor progression can be inhibited [235].…”

“…Fasting diets are currently in clinical trial to enhance chemotherapy efficacy and reduce toxicity however there is also evidence they may slow tumor progression [235]. In the fasting state IGF-1, a promoter of EMT, is inhibited, and clinical trials are underway to investigate if tumor progression can be inhibited [235]. Obesity induces lung neutrophilia leading to increased breast cancer lung metastasis through GM-CSF and IL-5 signaling.…”

Prospects for Radiopharmaceuticals as Effective and Safe Therapeutics in Oncology and Challenges of Tumor Resistance to Radiotherapy

“…In this regard, despite being debatable and largely rejected in some standard oncology practices, the therapeutic effects of short-term fasting during anticancer therapy should be discussed. [56][57][58][59] Clinical studies confirmed that when conducted exclusively under medical supervision and after careful assessment of the patient's condition (early-stage cancer with no signs of severe weight loss, diabetes, sarcopenia, cachexia or eating disorders), short-term water-only fasting just before and after radiotherapy could enhance the cytotoxic effects on the tumor cells at many levels. 56 Such an additional metabolic therapy contributes to the increased stress on oncogene-driven tumor cells during chemo/ radio therapy-it reduces the amount of their main source of energy and building blocks for growth, DNA repair and poliferation, gradually weakening all anti-apoptotic signaling pathways maintained by nutrition.…”