Early downmodulation of tumor glycolysis predicts response to fasting-mimicking diet in triple-negative breast cancer patients.

Autor:	Ligorio F; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; IFOM ETS, the AIRC Institute of Molecular Oncology, Via Adamello 16, 20139 Milan, Italy., Vingiani A; Oncology and Hematology-Oncology Department, University of Milan, Via Festa del Perdono 7, 20122 Milano, Italy; Department of Advanced Diagnostics, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Torelli T; Department of Advanced Diagnostics, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Sposetti C; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; Oncology and Hematology-Oncology Department, University of Milan, Via Festa del Perdono 7, 20122 Milano, Italy., Drufuca L; IFOM ETS, the AIRC Institute of Molecular Oncology, Via Adamello 16, 20139 Milan, Italy., Iannelli F; Haematopathogy Division, IEO, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141 Milan, Italy., Zanenga L; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Depretto C; Department of Radiology and Radiotherapy, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Folli S; Surgical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Scaperrotta G; Department of Radiology and Radiotherapy, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Capri G; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Bianchi GV; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Ferraris C; Surgical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Martelli G; Surgical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Maugeri I; Surgical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Provenzano L; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; Oncology and Hematology-Oncology Department, University of Milan, Via Festa del Perdono 7, 20122 Milano, Italy., Nichetti F; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Agnelli L; Department of Advanced Diagnostics, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Lobefaro R; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Fucà G; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Fotia G; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Mariani L; Unit of Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Morelli D; Department of Advanced Diagnostics, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Ladisa V; Hospital Pharmacy, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., De Santis MC; Department of Radiology and Radiotherapy, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Lozza L; Department of Radiology and Radiotherapy, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Trecate G; Department of Radiology and Radiotherapy, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Belfiore A; Department of Advanced Diagnostics, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Brich S; Department of Advanced Diagnostics, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Bertolotti A; Department of Advanced Diagnostics, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Lorenzini D; Oncology and Hematology-Oncology Department, University of Milan, Via Festa del Perdono 7, 20122 Milano, Italy; Department of Advanced Diagnostics, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Ficchì A; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Martinetti A; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Sottotetti E; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Arata A; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Corsetto P; Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy., Sorrentino L; Surgical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Rediti M; IFOM ETS, the AIRC Institute of Molecular Oncology, Via Adamello 16, 20139 Milan, Italy., Salvadori G; IFOM ETS, the AIRC Institute of Molecular Oncology, Via Adamello 16, 20139 Milan, Italy., Minucci S; Oncology and Hematology-Oncology Department, University of Milan, Via Festa del Perdono 7, 20122 Milano, Italy; Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Via Adamello 16, 20139 Milan, Italy., Foiani M; IFOM ETS, the AIRC Institute of Molecular Oncology, Via Adamello 16, 20139 Milan, Italy; Oncology and Hematology-Oncology Department, University of Milan, Via Festa del Perdono 7, 20122 Milano, Italy., Apolone G; Scientific Directorate, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Pagani M; IFOM ETS, the AIRC Institute of Molecular Oncology, Via Adamello 16, 20139 Milan, Italy; Department of Medical Biotechnology and Translational Medicine, University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy., Pruneri G; Oncology and Hematology-Oncology Department, University of Milan, Via Festa del Perdono 7, 20122 Milano, Italy; Department of Advanced Diagnostics, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., de Braud F; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; Oncology and Hematology-Oncology Department, University of Milan, Via Festa del Perdono 7, 20122 Milano, Italy., Vernieri C; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; IFOM ETS, the AIRC Institute of Molecular Oncology, Via Adamello 16, 20139 Milan, Italy. Electronic address: claudio.vernieri@istitutotumori.mi.it.
Jazyk:	angličtina
Zdroj:	Cell metabolism [Cell Metab] 2024 Dec 17. Date of Electronic Publication: 2024 Dec 17.
DOI:	10.1016/j.cmet.2024.11.004
Abstrakt:	In preclinical experiments, cyclic fasting-mimicking diets (FMDs) showed broad anticancer effects in combination with chemotherapy. Among different tumor types, triple-negative breast cancer (TNBC) is exquisitely sensitive to FMD. However, the antitumor activity and efficacy of cyclic FMD in TNBC patients remain unclear. Here, we show that a severely calorie-restricted, triweekly, 5-day FMD regimen results in excellent pathologic complete response (pCR) rates (primary endpoint) and long-term clinical outcomes (secondary endpoints) when combined with preoperative chemotherapy in 30 patients with early-stage TNBC enrolled in the phase 2 trial BREAKFAST. Bulk and single-cell RNA sequencing analysis revealed that highly glycolytic cancer cells, myeloid cells, and pericytes from tumors achieving pCR undergo a significant, early downmodulation of pathways related to glycolysis and pyruvate metabolism. Our findings pave the wave for conducting larger clinical trials to investigate the efficacy of cyclic FMD in early-stage TNBC patients and to validate early changes of intratumor glycolysis as a predictor of clinical benefit from nutrient restriction. This study was registered at Clinicaltrials.gov (NCT04248998). Competing Interests: Declaration of interests The authors declare the following competing interests: G.V.B., speaker/advisory board: Novartis, Eli Lilly, Daichi/Astrazeneca, Roche, MSD, and Seagen; G.P., consulting fees: Roche, Bayer, and Astra Zeneca; C.V., consulting fees/advisory board: Novartis, Pfizer, Eli Lilly, Daiichi Sankyo, and Menarini Stemline; C.V., honoraria as speaker: Novartis, Eli Lilly, Istituto Gentili, Accademia Nazionale di Medicina, MSD, Research grant: Roche; F.d.B., consulting fees/advisory board: Roche, EMD Serono, NMS Nerviano Medical Science, Sanofi, MSD, Novartis, Incyte, BMS, Menarini, Astra Zeneca, Pierre Fabre, Mattioli 1885, MCCann Health, Taiho; F.d.B., IQVIA Speaker Bureau: BMS, Healthcare Research & Pharmacoepidemiology, Merck Group, MSD, Pfizer, Servier, Sanofi, Roche, AMGEN, Incyte, Dephaforum, Seagen, Nadirex, BMS, Ambrosetti, and Itanet; and F.d.B., research grant/funding: Novartis, F.Hoffmann-LaRoche Ltd, BMS, Ignyta Inc., Merck Sharp & Dohme Spa, Kymab, Pfizer, Tesaro, MSD, MedImmune LCC, Exelixis Inc., LOXO Oncology Inc., DAICHI SANKIO Dev. Ltd, Basilea Pharmaceutica International AG, Janssen-Cilag International NV, and Merck KGAA. C.V. and F.d.B. are co-inventors of the FMD regimen used in this study. The Italian patent (no. 102019000009954) has been released and was first deposited on June 24(th), 2019, with an extension granted under PCT WO 2020/261131 on June 24(th), 2020. The European patent (no. 207403399), Canadian patent (no. 2144217), and USA patent are pending. (Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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