Acquired resistance in NSCLC: the journey from clinical definition to molecular understanding

The treatment of metastatic non-small-cell lung cancer (NSCLC) has improved substantially over the past 20 years, first with targeted therapy, and more recently with immune checkpoint inhibition (ICI) therapy. In this issue of Annals of Oncology, Schoenfeld et al. elucidate a consensus report on a possible definition of acquired resistance to ICI therapy in patients with metastatic NSCLC.1 This is a bit more than 10 years after Jackman et al. made a similar attempt to define acquired resistance to targeted therapy with tyrosine kinase inhibitors (TKIs) for NSCLC with an activating mutation in the EGFR gene.