BUB1 inhibition sensitizes lung cancer cell lines to radiotherapy and chemoradiotherapy
Background: Lung cancer is a major public health concern, with high incidence and mortality. Despite advances in targeted therapy and immunotherapy, microtubule stabilizers (paclitaxel, docetaxel), DNA intercalating platinum drugs (cisplatin) and radiation therapy continue to play a critical role in the management of locally advanced and metastatic lung cancer. Novel molecular targets would provide opportunities for improving the efficacies of radiotherapy and chemotherapy. Hypothesis: We hypothesize that BUB1 (Ser/Thr kinase) is over-expressed in lung cancers and that its inhibition will sensitize lung cancers to chemoradiation. Methods: BUB1 inhibitor (BAY1816032) was combined with platinum (cisplatin), microtubule poison (paclitaxel), a PARP inhibitor (olaparib) and radiation in cell proliferation and radiation sensitization assays. Biochemical and molecular assays were used to evaluate their impact on DNA damage signaling and cell death mechanisms. Results: BUB1 expression assessed