ONC201 enhances the radiosensitivity of small-cell lung cancer via inhibition of the FAK signaling pathway

Abstract

Summary Small-cell lung cancer (SCLC) is a highly aggressive neuroendocrine malignancy with a poor prognosis. Radiotherapy is an essential treatment strategy for SCLC but is constrained by rapid relapse and therapeutic resistance. ONC201, an orally bioavailable imipridone compound, has demonstrated clinical efficacy against various malignancies. This study explored the therapeutic potential of ONC201 as a radiosensitizer in SCLC. Our results showed that ONC201 significantly suppressed SCLC cell proliferation, migration, and invasion, while promoting cell-cycle arrest and apoptosis. Moreover, ONC201 enhanced cellular radiosensitivity, augmented radiotherapy-induced G2/M phase arrest, and promoted apoptosis. Mechanistically, we confirmed that ONC201 enhanced radiosensitivity by suppressing focal adhesion kinase (FAK) signaling. Overall, our findings underscore the potential of ONC201 as a promising radiosensitizer for SCLC treatment.