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Glioma Stem-like Cells (GSC) are one of the integral parts of Glioblastoma (GBM) and are generally resistant to standard cancer therapy. Radiation therapy is the standard therapy for GBM which improves the survival of patients and GSCs pose a major obstacle in radiation-induced cell death. Though transcriptomic landscape of different GSCs and their radiation response were well studied, the differences in bio-molecular composition are yet to be explored. Raman microspectroscopy being a non-invasive, label free technique, aids to determine the biomolecular constituent of cells at live conditions. Using GSCs with varying radiation sensitivity (training set), we identified inherent Raman spectral signatures specific to different levels of radiation sensitivity. Moreover, tracking irradiation induced changes in GSCs also identified signatures specific to radiation sensitivity. Both inherent and radiation induced signatures predicted the radiation sensitivity with very high accuracy in the test set. Integrated analysis of inherent and radiation-induced alterations through Raman spectroscopy identified differential regulation of several molecules, in particular glycogen, choline and cholesterol between GSCs with different radio sensitivity. Finally, we reversed the resistant phenotype by using small molecule inhibitors specific for the metabolic pathways of these biomolecules. Thus, we have found Raman spectral signatures to predict radiation sensitivity of GSCs. Further, we also demonstrate radiation-induced molecular changes in the GSCs and methods to reverse radiation sensitivity by using small molecule inhibitors. These findings will have clinical application in radiosensitizing the GSCs. Efficient anti-tumor therapy can be attained with lower dosage of radiation along with these inhibitors with less side-effects.
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