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Integrated metabolic analysis reveals cancer’s energy secrets

As normal cells transform into cancer cells, they require a large supply of energy in the form of ATP. Using the same pathway as normal cells would generate excessive heat, causing an overheating state. To prevent this, cancer cells appear to rely on a less efficient pathway that generates less heat. Credit: Metabolic Engineering (2025). DOI: 10.1016/j.ymben.2025.08.002

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. The article is titled “Metabolic flux and flux balance analyses indicate the relevance of metabolic thermogenesis and aerobic glycolysis in cancer cells.”

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.

Integrated metabolic analysis reveals cancer's energy secrets
In this study, a principle of cancer cell metabolism was elucidated by integrating 13C-metabolic flux analysis with flux balance analysis. The findings reveal that glycolysis-dependent, less efficient metabolism plays a role in reducing metabolic heat production compared to highly efficient oxidative phosphorylation. Credit: Metabolic Engineering (2025). DOI: 10.1016/j.ymben.2025.08.002

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.

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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, said, “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.

More information:
Nobuyuki Okahashi et al, Metabolic flux and flux balance analyses indicate the relevance of metabolic thermogenesis and aerobic glycolysis in cancer cells, Metabolic Engineering (2025). DOI: 10.1016/j.ymben.2025.08.002

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University of Osaka


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Integrated metabolic analysis reveals cancer’s energy secrets (2025, September 16)
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