Cancer cells can change the way they use energy, and these metabolic changes often make treatments less effective. Different tumors—and even different cells within the same tumor—can behave very differently, especially when they experience low oxygen levels, a condition known as hypoxia. Hypoxia is common in solid tumors and strongly influences how cancer cells grow, survive, and respond to drugs. However, scientists have lacked simple, scalable tools to study how individual cancer cells adjust their metabolism under hypoxic conditions.

In this study, we introduce a new laboratory method called the micro-metabolic rewiring (muMeRe) assay. This tool allows researchers to recreate low-oxygen conditions naturally produced by the cancer cells themselves, without needing complex equipment. This makes it possible to observe how different cancer cells generate hypoxia and shift their metabolism in response. We also created new ways to measure how flexible each cell type is in changing its metabolic behavior. Using this system, we tested a treatment designed to target cancer metabolism and showed that it can reduce drug resistance caused by hypoxia. Overall, this work provides a powerful new platform to help develop more effective, personalized cancer therapies.