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MicroRNA-Based Therapy in Animal Models of Selected Gastrointestinal Cancers

View Article: PubMed Central - PubMed

ABSTRACT

Gastrointestinal cancer accounts for the 20 most frequent cancer diseases worldwide and there is a constant urge to bring new therapeutics with new mechanism of action into the clinical practice. Quantity of in vitro and in vivo evidences indicate, that exogenous change in pathologically imbalanced microRNAs (miRNAs) is capable of transforming the cancer cell phenotype. This review analyzed preclinical miRNA-based therapy attempts in animal models of gastric, pancreatic, gallbladder, and colorectal cancer. From more than 400 original articles, 26 was found to assess the effect of miRNA mimics, precursors, expression vectors, or inhibitors administered locally or systemically being an approach with relatively high translational potential. We have focused on mapping available information on animal model used (animal strain, cell line, xenograft method), pharmacological aspects (oligonucleotide chemistry, delivery system, posology, route of administration) and toxicology assessments. We also summarize findings in the field pharmacokinetics and toxicity of miRNA-based therapy.

No MeSH data available.


Related in: MedlinePlus

Strategies in miRNA-based therapy. The most frequently used animal model of cancer is immunodeficient mouse bearing a subcutaneous tumor created from cells of human origin. In miRNA-based therapy, two concepts are adopted nowadays, which is the replacement therapy (left) and inhibition therapy (right). Tumor suppressors MiRNAs are decreased in cancer cells and to increase their levels mature miRNAs, miRNA-mimics, precursors, or expression vectors are administered. Oncogenic miRNAs are abundant in cancer tissue and to silence their effects, various types of miRNA inhibitors could be administered.
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Figure 3: Strategies in miRNA-based therapy. The most frequently used animal model of cancer is immunodeficient mouse bearing a subcutaneous tumor created from cells of human origin. In miRNA-based therapy, two concepts are adopted nowadays, which is the replacement therapy (left) and inhibition therapy (right). Tumor suppressors MiRNAs are decreased in cancer cells and to increase their levels mature miRNAs, miRNA-mimics, precursors, or expression vectors are administered. Oncogenic miRNAs are abundant in cancer tissue and to silence their effects, various types of miRNA inhibitors could be administered.

Mentions: To reverse the pathologic imbalance of miRNAs mature miRNAs, miRNA-mimics, precursors, or expression vectors are administered to increase the level of a specific tumor-suppressor miRNA, and miRNA inhibitors are administered to decrease the level of oncogenic miRNA (Figure 3). Promising results of in vitro studies are nowadays being verified on animal models and first preclinical, or even clinical trials are under way.


MicroRNA-Based Therapy in Animal Models of Selected Gastrointestinal Cancers
Strategies in miRNA-based therapy. The most frequently used animal model of cancer is immunodeficient mouse bearing a subcutaneous tumor created from cells of human origin. In miRNA-based therapy, two concepts are adopted nowadays, which is the replacement therapy (left) and inhibition therapy (right). Tumor suppressors MiRNAs are decreased in cancer cells and to increase their levels mature miRNAs, miRNA-mimics, precursors, or expression vectors are administered. Oncogenic miRNAs are abundant in cancer tissue and to silence their effects, various types of miRNA inhibitors could be administered.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037200&req=5

Figure 3: Strategies in miRNA-based therapy. The most frequently used animal model of cancer is immunodeficient mouse bearing a subcutaneous tumor created from cells of human origin. In miRNA-based therapy, two concepts are adopted nowadays, which is the replacement therapy (left) and inhibition therapy (right). Tumor suppressors MiRNAs are decreased in cancer cells and to increase their levels mature miRNAs, miRNA-mimics, precursors, or expression vectors are administered. Oncogenic miRNAs are abundant in cancer tissue and to silence their effects, various types of miRNA inhibitors could be administered.
Mentions: To reverse the pathologic imbalance of miRNAs mature miRNAs, miRNA-mimics, precursors, or expression vectors are administered to increase the level of a specific tumor-suppressor miRNA, and miRNA inhibitors are administered to decrease the level of oncogenic miRNA (Figure 3). Promising results of in vitro studies are nowadays being verified on animal models and first preclinical, or even clinical trials are under way.

View Article: PubMed Central - PubMed

ABSTRACT

Gastrointestinal cancer accounts for the 20 most frequent cancer diseases worldwide and there is a constant urge to bring new therapeutics with new mechanism of action into the clinical practice. Quantity of in vitro and in vivo evidences indicate, that exogenous change in pathologically imbalanced microRNAs (miRNAs) is capable of transforming the cancer cell phenotype. This review analyzed preclinical miRNA-based therapy attempts in animal models of gastric, pancreatic, gallbladder, and colorectal cancer. From more than 400 original articles, 26 was found to assess the effect of miRNA mimics, precursors, expression vectors, or inhibitors administered locally or systemically being an approach with relatively high translational potential. We have focused on mapping available information on animal model used (animal strain, cell line, xenograft method), pharmacological aspects (oligonucleotide chemistry, delivery system, posology, route of administration) and toxicology assessments. We also summarize findings in the field pharmacokinetics and toxicity of miRNA-based therapy.

No MeSH data available.


Related in: MedlinePlus