(355d) Probing Metabolic Changes in Cancer with Raman Spectroscopy in Response to Treatment, and Validated with Mass Spectrometry

Rapid and accurate response to targeted therapies is critical to differentiate tumors that are resistant to treatment early in the regimen. In this talk, I will demonstrate a recent work by my group where we show a rapid, noninvasive, and label-free approach to evaluate metabolic changes in breast cancer (BC) cells with Raman spectroscopy (RS) in response to treatment with molecular inhibitors. We applied multivariate analysis to RS data to classify the cells into responsive or nonresponsive groups as a function of drug dosage, drug type, and cell type. Metabolites identified with RS were then validated with mass spectrometry (MS), a gold standard in metabolism. We treated triple-negative BC cells with Trametinib, an inhibitor of the extracellular-signal-regulated kinase (ERK) pathway. Changes measured with both RS and MS corresponding to membrane phospholipids, amino acids, lipids and fatty acids indicated that these BC cells were responsive to treatment. Comparatively, minimal metabolic changes were observed post-treatment with Alpelisib, an inhibitor of the mammalian target of rapamycin (mTOR) pathway, indicating treatment resistance. These findings were corroborated with cell viability assay and immunoblotting. We also showed estrogen receptor-positive MCF-7 cells were nonresponsive to Trametinib with minimal metabolic and viability changes. Our findings support that oncometabolites identified with RS will ultimately enable rapid drug screening ensuring patients receive the most effective treatment at the earliest time point.