vx-970 and Neoplasm-Metastasis

M6620, a selective ATP-competitive inhibitor of the ATM and RAD3-related (ATR) kinase, is currently under investigation with radiation in patients with non-small cell lung cancer (NSCLC) brain metastases. We evaluated the DNA damage response (DDR) pathway profile of NSCLC and assessed the radiosensitizing effects of M6620 in a preclinical NSCLC brain metastasis model. Mutation analysis and transcriptome profiling of DDR genes and pathways was performed on NSCLC patient samples. NSCLC cell lines were assessed with proliferation, clonogenic survival, apoptosis, cell cycle, and DNA damage signaling and repair assays. NSCLC brain metastasis patient-derived xenograft models were used to assess intracranial response and overall survival.

Topics: Animals; Carcinoma, Non-Small-Cell Lung; Female; Heterografts; Humans; Isoxazoles; Lung Neoplasms; Mice; Mice, Nude; Neoplasm Metastasis; Pyrazines; Treatment Outcome