Cyclic Fasting–Mimicking Diet Plus Bortezomib and Rituximab Is an Effective Treatment for Chronic Lymphocytic Leukemia
A study in mouse and cell models of chronic lymphocytic leukemia, alongside a report on two patients.
Cancer Res, 2024. Raucci F, et al.
Funding and competing interests (from the paper, shortened): F. Raucci reports a patent for PCT/EP2016/072467 pending. C. Vernieri reports personal fees and other support from Novartis and Eli Lilly; other support from Pfizer, Menarini, and Daiichi Sankyo; personal fees from Istituto Gentili, Accademia di Medicina, and grants from Roche outside the submitted work; in addition, C. Vernieri has a patent; Italian patent released [first deposited Italian patent n. 102019000009954 (24th June 2019); Extension PCT WO 2020/261131 24th June 2020; European Patent n. 20740399 (pending); Canadian patent n. 2,144,217 (pending); international patent request n. PCT/IT2020/000083. Deposited on Dec 17, 2020 (pending)]. M. Di Tano reports a patent 20210352950 pending. R. Buono reports a patent pending. F. de Braud reports personal fees from Bristol Myers Squibb, Roche, Merck & Co, Bayer, Ignyta, Dephaforum, Biotechespert, Pfizer, Nadirex, Ambrosetti, Incyte, Motore Sanité, Events, Fare Comunicazione, Itanet, ESO, Ambrosetti, Accmed, Idea-z, Dynamicom Education, Tiziana Life Sciences, Celgene, Novartis, Pharm Research Associated, Daiichi Sankyo, Ignyta, Pfizer, Octimet Oncology, Pierre Fabre, Eli Lilly, Roche, AstraZeneca, Gentili, Fondazione Menarini, Sanofi, Taiho, Pierre Fabre, NMS, The healthcare business of Merck KGaA, Darmstadt, Kymab, Pfizer, and Tesaro; other support from Novartis, F. Hoffmann-LaRoche Ltd., Bristol Myers Squibb, Ignyta Operating Inc., Merck Sharp & Dohme Spa, Kymab, Pfizer, Tesaro, MSD, MedImmune LCC, Exelixis Inc., LOXO Oncology Incorporated, DAICHI SANKIO Dev. Limited, Basilea Pharmaceutica International AG, Janssen-Cilag International NV, Merck KGAA; personal fees and other support from Bristol Myers Squibb, Pierre Fabre, Mattioli 1885, MCCann Health, MSD, IQVIA; other support from Bristol Myers Squibb, Roche, Celgene, Amgen, and Sanofi outside the submitted work. V.D. Longo reports grants from AIRC during the conduct of the study; nonfinancial support from L-Nutra outside the submitted work; in addition, V.D. Longo has a patent for 15/761,287 pending. No disclosures were reported by the other authors.
- Study type
- Animal study (mice), with reported outcomes in 2 patients
- Journal
- Cancer Res
- Published
- 2024
- Authors
- Raucci F, et al.
- DOI
- 10.1158/0008-5472.can-23-0295
- PubMed ID
- 38241703
Summary
The authors describe the outcome of Fasting Mimicking Diet (FMD) cycles in two patients with chronic lymphocytic leukemia, and then investigate fasting and FMD cycles in mouse and cell models of the disease. In the laboratory work they measured cytotoxic and apoptotic effects, insulin and IGF1 concentrations and proteasome activity, combined fasting conditions with the proteasome inhibitor bortezomib in cell culture, and combined cyclic fasting or FMD with bortezomib and the anti-CD20 antibody rituximab in mice.
The authors state that they report on the outcome of the diet cycles in the two patients, and the abstract does not say what those outcomes were. In the models, they reported that fasting-mimicking conditions had mild cytotoxic effects that activated apoptosis, mediated in part by lowered insulin and IGF1 concentrations. They reported that leukemia cells increased proteasome activity under fasting conditions as an escape pathway, that adding bortezomib strongly increased the pro-apoptotic effect in cell culture, and that combining cyclic fasting or FMD with bortezomib and rituximab delayed disease progression and prolonged survival in mice. They say the strategy should be tested in clinical trials.
The findings here come from mouse models and from cells in culture, not from patients, and this is not a study of Prolon. The human element is two patients, with no comparison group, and the abstract states no outcome for them. The survival effect in mice required two cancer drugs alongside the diet, so the contribution of the diet on its own is not separated out. The authors state that clinical testing has yet to be done.
These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.
