Clinical approach of intratumoral heterogeneity in lung adenocarcinoma. Two clinical cases with changing somatic driver mutations

Cancer is a dynamic process of somatic evolution. Distinct cell populations that undergo mutations, result in positive or negative selection depending on whether or not these mutations confer an advantage over other cells. In current clinical practice, predictive biomarkers such as EGFR mutation and ALK rearrangement are used routinely for treatment making decisions in non-small cell lung cancer (NSCLC). However, pressure from targeted therapies increases positive selection of resistant clones, eventually resulting in resistance to the drug. Monitoring the mutation pattern during the disease's course may allow the most suitable therapeutic approach to be selected. Here we report two clinical cases with lung adenocarcinoma demonstrating discordance in oncogene driver mutations between primary site and subsequent metastasis, and how this has contributed to therapeutic decisions.