Integrated metabolic analysis reveals cancer's energy secrets

Osaka, Japan – A research group led by The University of Osaka has developed a novel method for analyzing cancer metabolism, revealing new insights into cancer's inefficient energy process. This breakthrough, published in Metabolic Engineering, combines biological experiments with advanced information science techniques to uncover the role of cancer-specific inefficient metabolism.

Cancer cells are characterized by their increased glucose uptake, a phenomenon known as the Warburg effect. While this increased glucose consumption would seemingly provide ample fuel for the energy demands of uncontrolled cell division, cancer cells utilize this glucose inefficiently, favoring aerobic glycolysis (a less energy-productive metabolic pathway) even when sufficient oxygen is available for more efficient oxidative phosphorylation. The reasons behind this seemingly paradoxical preference for less efficient energy production remain incompletely understood, and the precise mechanisms driving this metabolic shift are still being investigated. Existing methods for metabolic analysis often struggle to fully elucidate these cancer-specific pathways due to the inherent complexities of cellular metabolism.

This research employs a unique approach, combining metabolic flow analysis with computational modeling. This involved using stable isotope tracing to track the fate of glucose and reveal how it is processed within cells. The computational model then integrated these experimental findings to predict the flow of metabolism through various pathways, providing a key factor that can reproduce the cancer-specific metabolism in computer simulation. The results suggest that inefficient cancer metabolism can reduce heat generation for energy acquisition.

Understanding the unique metabolic characteristics of cancer cells is crucial for developing effective cancer treatments. This research provides a powerful new tool for identifying metabolic vulnerabilities that can be targeted by novel therapeutics. This could lead to the development of more effective and personalized cancer treatments with fewer side effects.

Dr. Nobuyuki Okahashi, lead author of this study emphasizes the potential of this research, "Our integrated approach allows us to gain a much deeper understanding of the metabolic reprogramming that occurs in cancer. We believe this will pave the way for the development of innovative therapeutic strategies targeting cancer-specific metabolic pathways." The collaboration between Osaka and Kanazawa Universities highlights the importance of interdisciplinary research in tackling complex biological challenges.

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The article, “Metabolic flux and flux balance analyses indicate the relevance of metabolic thermogenesis and aerobic glycolysis in cancer cells,” was published in Metabolic Engineering at DOI: https://doi.org/10.1016/j.ymben.2025.08.002

About The University of Osaka

The University of Osaka was founded in 1931 as one of the seven imperial universities of Japan and is now one of Japan's leading comprehensive universities with a broad disciplinary spectrum. This strength is coupled with a singular drive for innovation that extends throughout the scientific process, from fundamental research to the creation of applied technology with positive economic impacts. Its commitment to innovation has been recognized in Japan and around the world. Now, The University of Osaka is leveraging its role as a Designated National University Corporation selected by the Ministry of Education, Culture, Sports, Science and Technology to contribute to innovation for human welfare, sustainable development of society, and social transformation.

Website: https://resou.osaka-u.ac.jp/en