Exceptional tumour responses to fasting-mimicking diet combined with standard anticancer therapies: A sub-analysis of the NCT03340935 trial

Ligorio, Francesca; Fucà, Giovanni; Provenzano, Leonardo; Lobefaro, Riccardo; Zanenga, Lucrezia; Vingiani, Andrea; Belfiore, Antonino; Lorenzoni, Alice; Alessi, Alessandra; Pruneri, Giancarlo; Braud, Filippo de; Vernieri, Claudio

doi:10.1016/j.ejca.2022.05.046

Cited by 31 publications

(30 citation statements)

References 23 publications

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“…Patients diagnosed with different cancers that fasted voluntarily during their chemotherapy treatments reported fewer side effects and showed that fasting regimens were well tolerated. In the NCT03340935 trial that enrolled 101 patients with different type of neoplasms, five patients with advanced disease achieved complete and long-lasting tumor responses when treated with cycles of FMD plus the standard treatment (84). Another clinical trial (NCT03595540) evaluated the effect of FMD cycles on patients' body composition and confirmed that FMD cycles are feasible and safe at low nutritional risk, with no negative impact on body composition and nutritional status in cancer patients.…”

Section: Starvation Fmd and Other Nutritional Approachesmentioning

confidence: 94%

Novel pharmacological and dietary approaches to target mTOR in B-cell acute lymphoblastic leukemia

2023

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High-risk subtypes of B-cell acute lymphoblastic leukemia (B-ALL) are frequently associated with aberrant activation of tyrosine kinases (TKs). These include Ph+ B-ALL driven by BCR-ABL, and Ph-like B-ALL that carries other chromosomal rearrangements and/or gene mutations that activate TK signaling. Currently, the tyrosine kinase inhibitor (TKI) dasatinib is added to chemotherapy as standard of care in Ph+ B-ALL, and TKIs are being tested in clinical trials for Ph-like B-ALL. However, growth factors and nutrients in the leukemia microenvironment can support cell cycle and survival even in cells treated with TKIs targeting the driving oncogene. These stimuli converge on the kinase mTOR, whose elevated activity is associated with poor prognosis. In preclinical models of Ph+ and Ph-like B-ALL, mTOR inhibitors strongly enhance the anti-leukemic efficacy of TKIs. Despite this strong conceptual basis for targeting mTOR in B-ALL, the first two generations of mTOR inhibitors tested clinically (rapalogs and mTOR kinase inhibitors) have not demonstrated a clear therapeutic window. The aim of this review is to introduce new therapeutic strategies to the management of Ph-like B-ALL. We discuss novel approaches to targeting mTOR in B-ALL with potential to overcome the limitations of previous mTOR inhibitor classes. One approach is to apply third-generation bi-steric inhibitors that are selective for mTOR complex-1 (mTORC1) and show preclinical efficacy with intermittent dosing. A distinct, non-pharmacological approach is to use nutrient restriction to target signaling and metabolic dependencies in malignant B-ALL cells. These two new approaches could potentiate TKI efficacy in Ph-like leukemia and improve survival.

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Section: Starvation Fmd and Other Nutritional Approachesmentioning

confidence: 94%

Novel pharmacological and dietary approaches to target mTOR in B-cell acute lymphoblastic leukemia

2023

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“…Many preclinical studies have confirmed that dietary intervention can alleviate chemotherapy-induced toxicity 387 and enhance the body’s anticancer immune surveillance during immunotherapy. 315 , 388 – 391 Relevant dietary strategies include fasting-mimicking diets(FMDs), 392 high-fiber diets, 315 , 393 and ketogenic diets. 388 FMDs such as cyclic fasting, low-carbohydrate diets and calorie restriction could reshape anticancer immunity in cancer patients by enriching IFN-γ, enhancing intratumoral Th1/cytotoxic responses, and inducing the contraction of regulatory T-cell compartments, and stimulating other immune signatures related to favorable clinical outcomes.…”

Section: Cancer-related Microorganisms and Effectorsmentioning

confidence: 99%

Role of the gut microbiota in anticancer therapy: from molecular mechanisms to clinical applications

Zhao

Mei

et al. 2023

Sig Transduct Target Ther

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In the past period, due to the rapid development of next-generation sequencing technology, accumulating evidence has clarified the complex role of the human microbiota in the development of cancer and the therapeutic response. More importantly, available evidence seems to indicate that modulating the composition of the gut microbiota to improve the efficacy of anti-cancer drugs may be feasible. However, intricate complexities exist, and a deep and comprehensive understanding of how the human microbiota interacts with cancer is critical to realize its full potential in cancer treatment. The purpose of this review is to summarize the initial clues on molecular mechanisms regarding the mutual effects between the gut microbiota and cancer development, and to highlight the relationship between gut microbes and the efficacy of immunotherapy, chemotherapy, radiation therapy and cancer surgery, which may provide insights into the formulation of individualized therapeutic strategies for cancer management. In addition, the current and emerging microbial interventions for cancer therapy as well as their clinical applications are summarized. Although many challenges remain for now, the great importance and full potential of the gut microbiota cannot be overstated for the development of individualized anti-cancer strategies, and it is necessary to explore a holistic approach that incorporates microbial modulation therapy in cancer.

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“…Study aims did not include clinical outcome parameters. However, Ligorio et al [34] reported on 5 of the 101 patients included, who presented with advanced or metastatic solid tumors and who unexpectedly achieved complete and long-lasting tumor remissions.…”

Section: Recent Clinical Trials In Cancer Patientsmentioning

confidence: 99%

Caloric restriction and fasting-mimicking diets in the treatment of cancer patients

Arends

2023

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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Purpose of review Different forms of caloric restriction for patients with cancer are widely advertised in lay circles, based mainly on promising preclinical experiments, while evidence from clinical trials is still preliminary. This review aims to present physiological responses to fasting and update knowledge on recently accumulated evidence from preclinical models and clinical trials. Recent findings Like other mild stressors, caloric restriction induces hormetic changes in healthy cells, which increase the tolerance to subsequent more severe stressors. While protecting healthy tissues, caloric restriction sensitizes malignant cells to toxic interventions because of their deficiencies in hormetic mechanisms, especially control of autophagy. In addition, caloric restriction may activate anticancer-directed immune cells and deactivate suppressive cells, thus increasing immunosurveillance and anticancer cytotoxicity. These effects may combine to increase the effectivity of cancer treatments while limiting adverse events. Though evidence obtained from preclinical models is promising, clinical trials in cancer patients so far have been preliminary. In clinical trials it will remain essential to avoid inducing or aggravating malnutrition. Summary Based on physiology and evidence from preclinical models, caloric restriction is a promising candidate as a potential combination partner for clinical anticancer treatment. However, large randomized clinical trials investigating effects on clinical outcome in patients with cancer are still lacking.

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Exceptional tumour responses to fasting-mimicking diet combined with standard anticancer therapies: A sub-analysis of the NCT03340935 trial

Cited by 31 publications

References 23 publications

Novel pharmacological and dietary approaches to target mTOR in B-cell acute lymphoblastic leukemia

Novel pharmacological and dietary approaches to target mTOR in B-cell acute lymphoblastic leukemia

Role of the gut microbiota in anticancer therapy: from molecular mechanisms to clinical applications

Caloric restriction and fasting-mimicking diets in the treatment of cancer patients

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