Reversing epigenetic mechanisms of drug resistance in solid tumors using targeted microRNA delivery.
Tumor cells utilize many different mechanisms to desensitize themselves to the cytotoxic effects of drugs, but it has recently been recognized that alterations in epigenetic control of gene expression underly many of them. As master regulators of gene expression, microRNAs (miRNAs) present a promising therapeutic strategy for the reversal of epigenetic changes that lead to drug resistance phenotypes in tumor cells.



Effects of epigenetic changes on drug resistance in a variety of solid tumors are discussed. Specific miRNAs that are involved with the regulation of epigenetic machinery are highlighted. Further, we consider how delivery of miRNA or antagomirs may be utilized to resensitize drug-resistant tumor cells.



Reversal of epigenetically controlled tumor drug resistance mechanisms via miRNA delivery presents a novel strategy for enhancing the efficacy of chemotherapeutics. Further, the ability to target delivery of miRNAs may provide the opportunity to go beyond reversal of resistance to hyper-sensitization of tumor cells to the cytotoxic effects of drugs. However, understanding of the role of miRNA in epigenetic regulation is still in its early stages and further research is critical for potential utility in improving therapeutic efficacy in cancer patients.
a Department of Pharmaceutical Sciences, School of Pharmacy , Northeastern University , Boston , MA , USA.
Melissa
M
Berman
a Department of Pharmaceutical Sciences, School of Pharmacy , Northeastern University , Boston , MA , USA.
George
G
Mattheolabakis
a Department of Pharmaceutical Sciences, School of Pharmacy , Northeastern University , Boston , MA , USA.
Megha
M
Suresh
a Department of Pharmaceutical Sciences, School of Pharmacy , Northeastern University , Boston , MA , USA.|b Faculty of Pharmacy , King Abdulaziz University , Jeddah , Saudi Arabia.
Mansoor
M
Amiji
D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D044127:Epigenesis, Genetic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology
D035683:MicroRNAs
Cancer epigenetics; chemotherapeutic; drug resistance; microRNA; nanoparticle