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Background Residual disease of glioblastoma (GBM) causes recurrence. However, targeting residual cells have failed due to their inaccessibility and our lack of understanding their survival mechanisms to radiation therapy. Here we deciphered residual cell specific survival mechanism essential for GBM relapse. Methods Therapy Resistant Residual (RR) cells were captured from primary patient samples and cell line models mimicking clinical scenario of radiation resistance. Molecular signaling of resistance in RR cells was identified using RNA