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MicroRNA Therapeutics in Cancer: Current Advances and Challenges

SIMPLE SUMMARY: Cancer is a complex disease associated with deregulation of numerous genes. In addition, redundant cellular pathways limit efficiency of monotarget drugs in cancer therapy. MicroRNAs are a class of gene expression regulators, which often function by targeting multiple genes. This fea...

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Detalles Bibliográficos
Autores principales: Reda El Sayed, Soha, Cristante, Justine, Guyon, Laurent, Denis, Josiane, Chabre, Olivier, Cherradi, Nadia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198729/
https://www.ncbi.nlm.nih.gov/pubmed/34072348
http://dx.doi.org/10.3390/cancers13112680
Descripción
Sumario:SIMPLE SUMMARY: Cancer is a complex disease associated with deregulation of numerous genes. In addition, redundant cellular pathways limit efficiency of monotarget drugs in cancer therapy. MicroRNAs are a class of gene expression regulators, which often function by targeting multiple genes. This feature makes them a double-edged sword (a) as attractive targets for anti-tumor therapy and concomitantly (b) as risky targets due to their potential side effects on healthy tissues. As for conventional antitumor drugs, nanocarriers have been developed to circumvent the problems associated with miRNA delivery to tumors. In this review, we highlight studies that have established the pre-clinical proof-of concept of miRNAs as relevant therapeutic targets in oncology. Particular attention was brought to new strategies based on nanovectorization of miRNAs as well as to the perspectives for their applications. ABSTRACT: The discovery of microRNAs (miRNAs) in 1993 has challenged the dogma of gene expression regulation. MiRNAs affect most of cellular processes from metabolism, through cell proliferation and differentiation, to cell death. In cancer, deregulated miRNA expression leads to tumor development and progression by promoting acquisition of cancer hallmark traits. The multi-target action of miRNAs, which enable regulation of entire signaling networks, makes them attractive tools for the development of anti-cancer therapies. Hence, supplementing downregulated miRNA by synthetic oligonucleotides or silencing overexpressed miRNAs through artificial antagonists became a common strategy in cancer research. However, the ultimate success of miRNA therapeutics will depend on solving pharmacokinetic and targeted delivery issues. The development of a number of nanocarrier-based platforms holds significant promises to enhance the cell specific controlled delivery and safety profile of miRNA-based therapies. In this review, we provide among the most comprehensive assessments to date of promising nanomedicine platforms that have been tested preclinically, pertaining to the treatment of selected solid tumors including lung, liver, breast, and glioblastoma tumors as well as endocrine malignancies. The future challenges and potential applications in clinical oncology are discussed.