(B-45) Metabolic response to platinum-based therapies in tumor spheroids and patient-derived organoids measured with Raman spectroscopy

Introduction:: Early and accurate prediction of resistance to cancer therapies is critical to determine the earliest time-point for therapeutic intervention for patient management. However, changes in tumor size is an inherently slow process. Metabolic reprogramming is a well-known hallmark of cancer and occurs much earlier than a change in tumor burden is seen. Therefore, highly sensitive, rapid, and low-cost diagnostic tools that allow us to track changes in multiple metabolites simultaneously in patient samples is highly desirable for clinical assessment.

Materials and Methods:: We use Raman spectroscopy to analyze the 4T1 cells, 4T1 spheroids and patient-derived organoids. Raman Spectroscopy is also a label-free, stain-free, and extraction-free method that allows direct measurement of samples without the need for costly and time-consuming preparation steps, and because it is nondestructive, samples can be archived for future study. All single and multi-cell cultures were treated using cisplatin at a concentration as considered from the cytotoxic assay.


Results, Conclusions, and Discussions:: Here we show Raman spectroscopy meets this clinical need, and is highly effective in monitoring metabolic rewiring in cancer cells, spheroids, and patient-derived organoids at the single cell level in response to cisplatin treatment. We found several classes of metabolites including lipids, nucleic acids, and amino acids as predictors of resistance/response in all three sample types. Unexpectedly, we also found that changes in metabolites significantly vary with the change in the depth of spheroids and organoids indicating heterogeneities in treatment response within the periphery and hypoxic core of spheroids and organoids. We also identified metabolic pathways through KEGG analysis that were either enriched or downregulated in response to cisplatin treatment. Our findings show that Raman spectroscopy is a powerful approach to track drug-induced metabolic changes and identify mechanisms of response to cancer treatment. We also demonstrate that the utility of 3D cell cultures and organotypic cultures recapitulates the therapeutic response in the patient tumor microenvironment.

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