Microscopy approach offers new way to study cancer therapeutics at single-cell level

Understanding how tumors change their metabolism to resist treatments is a growing focus in cancer research. As cancer cells adapt to therapies, their metabolism often shifts, which can help them survive and thrive despite medical interventions. This process, known as metabolic reprogramming, is a key factor in the development of treatment resistance. However, current methods to study these changes can be costly, complex, and often destructive to the cells being studied. Researchers at the University of Kentucky have developed a new, simpler approach to observe these metabolic shifts in cancer cells, offering a more accessible and effective tool for cancer research.

As reported in Biophotonics Discovery, the team developed a novel microscopy technique that uses a standard fluorescence microscope in combination with imaging software. This method allows scientists to observe and analyze metabolic changes in individual cancer cells, without the need for expensive equipment or destructive testing. In their experiments, the researchers focused on head and neck squamous cell carcinoma (HNSCC), a type of cancer that is often resistant to radiation therapy. They found that radiation treatment caused significant metabolic changes in the cells, particularly through the activation of a protein called HIF-1α, which helps cells adapt to low oxygen levels commonly found in tumors.

The team used commercially available metabolic probes to assess how different HNSCC cell lines reacted to radiation. They discovered that one cell line (rSCC-61) showed much higher levels of HIF-1α expression compared to another, suggesting a stronger metabolic shift towards radioresistance. By inhibiting HIF-1α, they were able to reverse some of these changes and make the radioresistant cells more sensitive to radiation.

This new technique could be a game-changer for researchers studying cancer metabolism. By using readily available, low-cost tools, scientists can now perform detailed single-cell analyses of metabolic changes in response to treatments, opening up new opportunities for understanding and overcoming treatment resistance in cancer.

Senior author Caigang Zhu remarks, “The study demonstrates the functional flexibility of our novel optical approach to report the key metabolic changes of radioresistant and radiosensitive HNSCC under therapeutics stress thereby revealing the role of metabolism reprogramming in the development of resistance to cancer therapeutics.”

Zhu notes that this approach was inspired by the practical challenges the team faced when trying to access expensive metabolic tools in the past. “This work was motivated by the practical barriers for the access to expensive metabolic tools we met in the past for tumor metabolism studies,” says Zhu. “Our demonstrations and results are exciting, as we now have a cost-effective approach to study cell metabolism at single-cell level with minimal expertise requirement.” 

The results of this study are promising for the future of cancer metabolism discoveries. A standard fluorescence microscope along with proper imaging processing techniques could be a powerful tool for studying the role of metabolic reprogramming in the development of resistance to cancer therapeutics at the single-cell level in a more efficient, cost-effective, and nondestructive manner. With this innovation, the study of tumor metabolism could become more accessible to a broader range of researchers.

For details, see the original Gold Open Access article by J. Yan, C. F. L. Goncalves, et al., “Optical imaging provides flowcytometry-like single-cell level analysis of HIF-1a-mediated metabolic changes in radioresistant head and neck squamous carcinoma cells,” Biophotonics Discovery 2(1), 012902 (2025), doi: 10.1117/1.BIOS.2.1.012702