Suda K, Murakami I, Obata K, et al. - Acquired resistance against targeted therapies represents a critical issue, so researchers assessed 128 specimens from 24 autopsied patients with lung adenocarcinoma harboring EGFR (epidermal growth factor receptor) mutation to analyze the frequency, clinical backgrounds, clinical implications, as well as patterns of spatial heterogeneity in resistance mechanisms to EGFR tyrosine kinase inhibitors (TKIs). Treatment with 1st/2nd generation EGFR-TKI was received by all patients and they demonstrated acquired resistance to the drug before death. In two cases, no resistance mechanism was found. Among 22 patients whose resistance mechanisms were detected, the presence of spatial heterogeneity of resistance mechanisms was found in ten; these patients were identified to have a significantly shorter time-to-treatment failure vs those without heterogeneity. In lung adenocarcinoma, the presence of significant spatial heterogeneity of acquired resistance mechanisms to EGFR-TKIs was seen in this study. As per the data, there may be variation in the incidence of resistance mechanisms based on the biopsied tumor locations.