AsianScientist (Mar. 13, 2015) – The microRNA miR-27b can enhance the effectiveness of chemotherapy drugs by simultaneously activating cell death and preventing drug detoxification in cancer cells. The study documenting these findings, published in Cell Research, could help prevent drug resistance and allow patients to be treated with lower drug doses.
Multidrug resistance is a major obstacle in treating advanced liver cancers and kidney cancers, both refractory to chemotherapeutic drugs and molecular-targeted drugs. Due to impaired liver and kidney functions in these patients, it is impractical to enhance therapeutic effect by increasing drug doses. Novel strategies to enhance the sensitivity of current anticancer drugs are urgently needed.
Because cancers are not dependent on a single pathway to develop resistance, an emerging trend is toward promoting the sensitivity by targeting multiple resistance pathways in parallel. Exploiting the multi-target characteristic of miRNAs, researchers led by Professor Hui Lijian at the Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences combined the miRNA miR-27b with anticancer drugs to enhance therapeutic responses.
miR-27b was identified by an unbiased screening and bioinformatic analyses. In vitro, miR-27b was found to sensitize cancer cells to a broad spectrum of anticancer drugs. Moreover, the combinational use of miR-27b and low dose of anticancer drugs showed a synergistic therapeutic effect with undetectable side effects in vivo.
The researchers found that miR-27b enhances drug sensitivity through a double-layer regulation, firstly by activating p53-dependent apoptosis and secondly by reducing CYP1B1-mediated drug detoxification. Based on these findings, the researchers proposed that miR-27b promotes a good drug response specifically in patients carrying p53-wild-type or CYP1B1-high gene signature, suggesting a personalized application of miR-27b and anticancer drugs to improve therapeutic effects.
The article can be found at: Mu et al. (2015) miR-27b Synergizes with Anticancer Drugs via p53 Activation and CYP1B1 Suppression.
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Source: Shanghai Institutes for Biological Sciences.
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