Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MRX34 has recently entered the clinic as the first therapeutic product based on a microRNA (miRNA) mimic. In order to measure drug concentrations in vivo, a quantitation method is needed that exhibits high precision, accuracy, and robustness. While most clinical applications for oligonucleotide therapeutics involve methods based on hybridization assays and liquid chromatography-tandem mass spectrometry, quantitative PCR (qPCR) is a less well-described approach. Here, we present an RT, qPCR, and analysis method to determine the tissue biodistribution of endogenous as well as a therapeutic, exogenous miRNA mimic therapeutic. Assay performance is demonstrated on multiple tissues from nonhuman primates dosed with MRX34.
Methods Mol Biol 2015
PMID:A qRT-PCR Method for Determining the Biodistribution Profile of a miR-34a Mimic. 2607 5

Colorectal cancer (CRC) is one of the leading cancer-related causes of death in the world. Several approaches such as surgery, chemotherapy, radiotherapy, targeted therapy, or combinations thereof have been used to treat CRC patients. However, the fact that many patients develop a drug resistance during the course of the treatment is a major obstacle. Understanding the mechanisms underlying resistance is critical in order to develop more effective targeted treatments. Recently, several studies have reported on the regulatory role of microRNAs (miRNAs) in the response to anti-cancer drugs and suggested them as a source of predictive biomarkers for the purpose of patient stratification and for the prognosis of treatment success. For example, overexpressing miR-34a, a master regulator of tumor suppression attenuates chemoresistance to 5-FU by downregulating silent information regulator 1 (SIRT1) and E2F3. MRX34, a miR-34a replacement is the first synthetic miRNA mimic to enter clinical testing. MiR-34a antagonizes cancer stemness, metastasis, and chemoresistance processes that are necessary for cancer viability. This example shows that miRNAs are coming into focus for the design of enhanced cancer therapies that aim to sensitise tumor cells for anti-cancer drugs. In this review, we provide an overview on the role of miRNAs in the resistance to current colorectal cancer therapies. Furthermore, we discuss the value of miRNAs as biomarkers for predicting chemosensitivity and their potential to enhance treatment strategies.
Cell Mol Biol (Noisy-le-grand) 2015 Oct 30
PMID:The role of microRNAs in the resistance to colorectal cancer treatments. 2651 92

Colorectal cancer (CRC) is among the main tumor-related causes of death worldwide. The fact that the majority of the patients develop resistance to chemoradiotherapy (CRT) is a major obstacle for the treatment of CRC. In order to develop more effective treatment strategies, it is crucial to elucidate the mechanisms underlying the development of resistance to CRT. Several studies have recently indicated the regulatory effects of microRNAs (miRNAs) in response to antitumor agents. For example, miR-34a attenuates the chemoresistance of colon cancer to 5-FU by inhibiting E2F3 and SIRT1. The miR-34a mimic MRX34 is the first synthetic miRNA to have been entered into clinical trials. miR-21 prevents tumor cell stemness, invasion and drug resistance, which are required for the development of CRC. These findings suggest that miRNAs represent a focus in the research of novel cancer treatments aimed at sensitizing cancer cells to chemotherapeutic drugs. The aim of the present study was to review the functions of miRNAs and investigate the roles of miRNAs in CRC radioresistance or chemoresistance. Furthermore, the potential of including miRNAs in therapeutic strategies and using them as molecular biomarkers for predicting radiosensitivity and chemosensitivity was discussed.
Mol Clin Oncol 2018 04
PMID:Role of microRNAs in the resistance of colorectal cancer to chemoradiotherapy. 2955 86