Combination of microRNA therapeutics with small-molecule anticancer drugs: Mechanism of action and co-delivery nanocarriers

MicroRNAs (miRNAs) regulate multiple molecular pathways vital for the hallmarks of cancer with a high degree of biochemical specificity and potency. By restoring tumor suppressive miRNAs or ablating oncomiRs, miRNA-based therapies can sensitize cancer cells to conventional cytotoxins and the molecularly targeted drugs by promoting apoptosis and autophagy, reverting epithelial-to-mesenchymal transition, suppressing tumor angiogenesis, and downregulating efflux transporters. The development of miRNA-based therapeutics in combination with small-molecule anticancer drugs provides an unprecedented opportunity to counteract chemoresistance and improve treatment outcome in a broad range of human cancers. This review summarizes the mechanisms and advantages for the combination therapies involving miRNAs and small-molecule drugs, as well as the recent advances in the co-delivery nanocarriers for these agents. (C) 2014 Elsevier B.V. All rights reserved.