The EACR’s Top 10 Cancer Research Publications is a regular summary of the most interesting and impactful recent papers in cancer research. It is curated by the Board of the European Association for Cancer Research (EACR).
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Vernieri et al., Cancer Discov January 1 2022 (12) (1) 90-107
Summary of the findings
In preclinical models, cyclic calorie restriction, in the form of fasting or fasting-mimicking diets (FMDs), has been shown to potentiate the antitumor effects of standard antineoplastic therapies, such as chemotherapy, endocrine therapy and immunotherapy, by affecting host/tumor metabolism and by boosting antitumor immunity. However, the applicability of this approach in clinical setting remains unclear.
In our Cancer Discovery paper, we reported the results of a first-in-human, phase Ib clinical trial in 101 cancer patients. We showed that a severely calorie-restricted 5-day FMD regimen is safe and well tolerated when repeated every three/four weeks in combination with standard antineoplastic treatments. The FMD resulted in a significant and consistent reduction of blood glucose, insulin and IGF-1 concentration, thus recapitulating the metabolic effects that were found to mediate in part the antitumor activity of calorie restriction in preclinical studies.
More importantly, the FMD produced a global and desirable reshaping of systemic and intratumor immunity, with a reduction of immunosuppressive immune cell subsets, including myeloid-derived suppressor cells, regulatory T cells and exhausted T cells, paralleled by an increase in cytotoxic/activated T cells, activated dendritic cells, cytolytic Natural Killer cells and memory T cells. Some of these immune modifications were maintained more than 30 days after the completion of the FMD.
Future impact of the findings
Based on 1) solid preclinical evidence showing consistent and synergistic antitumor effects of cyclic FMD and standard antitumor therapies and 2) our results demonstrating safety and desirable metabolic and immunologic effects of cyclic FMD in cancer patients, our group and other groups have recently initiated phase II clinical trials to investigate if cyclic FMD can improve the antitumor activity/efficacy of standard chemotherapy in selected cancer patient populations, such as in patients with LKB1-inactive advanced lung adenocarcinoma (FAME trial, NCT03709147) or in patients with early-stage triple-negative breast cancer (TNBC) (BREAKFAST trial, NCT04248998). These trials may provide first clinical evidence of antitumor activity of cyclic FMD in cancer patients.
