당질제한식(키토식단)과 췌장암에 대한 연구논문이 발표되어 소개합니다.
출처: Daniel Von Hoff et.al, "Ketogenic diet and chemotherapy
combine to disrupt pancreatic cancer metabolism and growth".
Med 3, 119-136,
Feb.11,2022.
Summary
Background
Ketogenic
diet is a potential means of augmenting cancer therapy. Here, we explore ketone
body metabolism and its interplay with chemotherapy in pancreatic cancer.
Methods
Metabolism
and therapeutic responses of murine pancreatic cancer were studied using KPC
primary tumors and tumor chunk allografts. Mice on standard high-carbohydrate
diet or ketogenic diet were treated with cytotoxic chemotherapy
(nab-paclitaxel, gemcitabine, cisplatin). Metabolic activity was monitored with
metabolomics and isotope tracing, including 2H- and 13C-tracers,
liquid chromatography-mass spectrometry, and imaging mass spectrometry.
Findings
Ketone
bodies are unidirectionally oxidized to make NADH. This stands in contrast to
the carbohydrate-derived carboxylic acids lactate and pyruvate, which rapidly
interconvert, buffering NADH/NAD. In murine pancreatic tumors, ketogenic diet
decreases glucose’s concentration and tricarboxylic acid cycle contribution,
enhances 3-hydroxybutyrate’s concentration and tricarboxylic acid contribution,
and modestly elevates NADH, but does not impact tumor growth. In contrast, the
combination of ketogenic diet and cytotoxic chemotherapy substantially
raises tumor NADH and synergistically suppresses tumor growth, tripling the
survival benefits of chemotherapy alone. Chemotherapy and ketogenic
diet also synergize in immune-deficient mice, although long-term growth
suppression was only observed in mice with an intact immune system.
Conclusions
Ketogenic
diet sensitizes murine pancreatic cancer tumors to cytotoxic chemotherapy.
Based on these data, we have initiated a randomized clinical trial of
chemotherapy with standard versus ketogenic diet for patients with metastatic
pancreatic cancer (NCT04631445).