意大利IRCCS肿瘤研究所Claudio Vernieri团队发现，肿瘤糖酵解的早期下调，可预测三阴性乳腺癌患者对模拟禁食饮食的反应。相关论文于2024年12月17日在线发表于国际学术期刊《细胞—代谢》。

研究人员发现，严重限制卡路里的每三周5天的模拟禁食饮食（FMD）方案与术前化疗联合使用，在30名早期三阴性乳腺癌（TNBC）患者中，取得了优异的病理完全反应（pCR）率（主要终点）和长期临床结局（次要终点）。

通过大规模和单细胞RNA测序分析，研究人员发现，来自达到pCR的肿瘤的高糖酵解癌细胞、髓系细胞和周围细胞，在早期经历了与糖酵解和丙酮酸代谢相关通路的显著下调。

该研究为开展更大规模的临床试验提供了基础，可用于调查周期性FMD在早期TNBC患者中的疗效，并验证肿瘤内糖酵解早期变化作为营养限制治疗临床获益的预测因子。该研究已在Clinicaltrials.gov注册（NCT04248998）。

研究人员表示，在临床前实验中，周期性FMD与化疗联合显示出广泛的抗癌效果。在不同的肿瘤类型中，TNBC对FMD的敏感性尤为突出。然而，周期性FMD在TNBC患者中的抗肿瘤活性和疗效仍不明确。

附：英文原文

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

Author: Francesca Ligorio, Andrea Vingiani, Tommaso Torelli, Caterina Sposetti, Lorenzo Drufuca, Fabio Iannelli, Lucrezia Zanenga, Catherine Depretto, Secondo Folli, Gianfranco Scaperrotta, Giuseppe Capri, Giulia V. Bianchi, Cristina Ferraris, Gabriele Martelli, Ilaria Maugeri, Leonardo Provenzano, Federico Nichetti, Luca Agnelli, Riccardo Lobefaro, Giovanni Fucà, Giuseppe Fotia, Luigi Mariani, Daniele Morelli, Vito Ladisa, Maria Carmen De Santis, Laura Lozza, Giovanna Trecate, Antonino Belfiore, Silvia Brich, Alessia Bertolotti, Daniele Lorenzini, Angela Ficchì, Antonia Martinetti, Elisa Sottotetti, Alessio Arata, Paola Corsetto, Luca Sorrentino, Mattia Rediti, Giulia Salvadori, Saverio Minucci, Marco Foiani, Giovanni Apolone, Massimiliano Pagani, Giancarlo Pruneri, Filippo de Braud, Claudio Vernieri

Issue&Volume: 2024-12-17

Abstract: 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).

DOI: 10.1016/j.cmet.2024.11.004

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(24)00450-9