A combinatorial microRNA therapeutics approach to suppressing non-small cell lung cancer

Targeted cancer therapies, while often effective, have limited utility due to preexisting primary or acquired secondary resistance. Consequently, agents are sometimes used in combination to simultaneously affect multiple targets. MicroRNA mimics are excellent therapeutic candidates because of their ability to repress multiple oncogenic pathways at once. Here we treated the aggressive Kras;p53 non-small cell lung cancer mouse model and demonstrated efficacy with a combination of two tumor-suppressive microRNAs. Systemic nano-delivery of miR-34 and let-7 suppressed tumor growth leading to a survival advantage. This combinatorial microRNA therapeutic approach engages numerous components of tumor-cell addictive pathways and highlights the ability to deliver multiple microRNAs in a safe and effective manner to target lung tissue.