Introduction: The treatment scenario of lung cancer is rapidly evolving through time. In parallel, growing evidence is accumulating on different mechanisms of treatment resistance. Inter- and intra-tumor heterogeneity define the spatial and temporal tumor clonal evolution, that is at the basis of tumor progression and resistance to anticancer treatments.Areas covered: This review summarizes the available evidence on molecular heterogeneity in lung cancer, from diagnosis to the occurrence of treatment resistance. The application of novel molecular diagnostic methods to detect molecular heterogeneity, and the implications of understanding heterogeneity for drug development strategies are discussed, with focus on clinical relevance and impact on patients' survival.Expert opinion: The current knowledge of molecular heterogeneity allows to identify different molecular subgroups of patients within the same conventional tumor type. Deeper understanding of heterogeneity determinants and the possibility to comprehensively investigate tumor molecular patterns will lead to the development of personalized treatment approaches, with the final goal to overcome resistance and prolong survival in lung cancer patients.
Keywords: Clonality; next-generation sequencing; resistance; tumor evolution; tyrosine kinase inhibitors.