Engineering microRNAs as multimodal cancer therapeutics

Resistance to systemic therapy remains a major challenge in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have improved outcomes for patients with EGFR-mutant tumors, but acquired resistance is common and can arise through diverse genetic and non-genetic mechanisms.1 This heterogeneity makes resistance difficult to address by targeting a single downstream pathway. In the previous issue of Molecular Therapy Nucleic Acids, Intriago and colleagues report a different approach by incorporating the nucleoside analog gemcitabine directly into the tumor-suppressive microRNA (miRNA) miR-129 (Figure 1).