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In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
MicroRNA-Based Therapy in Animal Models of Selected Gastrointestinal Cancers
Jana Merhautova1, Regina Demlova2, Ondrej Slaby3
1Molecular Oncology II - Solid Cancer, Central European Institute of Technology, Masaryk UniversityBrno, Czech Republic; Department of Pharmacology, Faculty of Medicine, Masaryk UniversityBrno, Czech Republic.
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.
Insights
Preclinical studies show that modifying microRNAs (miRNAs) can alter cancer cell behavior. This review analyzes miRNA-based therapies in animal models for gastrointestinal cancers, highlighting their translational potential.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Gastrointestinal cancers are a major global health concern, necessitating novel therapeutic strategies.
- MicroRNAs (miRNAs) are increasingly recognized for their role in cancer development and progression.
- Modulating miRNA expression presents a promising avenue for cancer treatment.
Approach:
- This review systematically analyzed preclinical studies (over 400 articles) investigating miRNA-based therapies in animal models for gastric, pancreatic, gallbladder, and colorectal cancers.
- 26 selected studies evaluated the efficacy of miRNA mimics, precursors, expression vectors, or inhibitors.
- The analysis focused on animal models, pharmacological aspects (oligonucleotide chemistry, delivery), administration routes, and toxicology.
Key Points:
- Exogenous manipulation of dysregulated miRNAs can reverse cancer cell phenotypes.
- Preclinical miRNA-based therapies demonstrate significant translational potential for gastrointestinal malignancies.
- Comprehensive data on animal models, drug delivery, pharmacokinetics, and toxicity were mapped.
Conclusions:
- miRNA-based therapeutics offer a promising, targeted approach for gastrointestinal cancer treatment.
- Further research into the pharmacokinetics and toxicology of miRNA therapies is crucial for clinical translation.
- This review provides a valuable resource for researchers and clinicians developing novel miRNA-based cancer treatments.
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