Imaging NRF2 activation in non-small cell lung cancer with positron emission tomography.

ABSTRACT: Mutations in the NRF2-KEAP1 pathway are common in non-small cell lung cancer (NSCLC) and confer broad-spectrum therapeutic resistance, leading to poor outcomes. Currently, there is no means to non-invasively identify NRF2 activation in living subjects. Here, we show that positron emission tomography imaging with the system x_c^- radiotracer, [¹⁸F]FSPG, provides a sensitive and specific marker of NRF2 activation in orthotopic, patient-derived, and genetically engineered mouse models of NSCLC. We found a NRF2-related gene expression signature in a large cohort of NSCLC patients, suggesting an opportunity to preselect patients prior to [¹⁸F]FSPG imaging. Furthermore, we reveal that system x_c^- is a metabolic vulnerability that can

SUBMITTER: Greenwood HE 

PROVIDER: S-EPMC11652680 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature