Topics in Anti-Cancer Research

Topics in Anti-Cancer Research

Volume: 6

Indexed in: Chemical Abstracts, EBSCO, Ulrich's Periodicals Directory.

Topics in Anti-Cancer Research covers important advances on both experimental (preclinical) and clinical cancer research in drug development. The book series offers readers an insight into current ...
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Recent Advances and Challenges in microRNABased Cancer Therapeutics

Pp. 178-210 (33)

Amjad Ali, Faryal M. Awan, Aqsa Ikram and Shifa T. Ashraf

Abstract

Despite significant advancements in understanding the cancer-associated signaling cascades, effective treatment strategies remain scarce. This intricacy of cancer enigma highlights a pressing need to develop novel therapeutics. The seminal discovery of microRNAs (miRNAs), a class of natural RNA-interfering agents, provides a new hope for accomplishing this task. Bolstered by a novel mode of action, the ability to function as tiny master regulators of cellular processes, ease of administration and sufficient uptake along with apparent lack of toxicity in normal tissues give miRNAs an extra edge and make them an ideal candidate for emerging therapeutic developments. Genome-wide investigations have shown more than half of the human miRNA genes being located on genomic regions or at fragile sites associated with cancer, unveiling the substantial significance of these small RNAs. Very soon after the discovery of the first miRNA, miRNA-based therapeutics has entered clinical trials and has shown fascinating results in preclinical development. This rapid progress through the discovery pipeline into clinical development imitates the significance of miRNAs as critical regulators in human diseases, and holds the pledge of yielding a novel class of therapeutics that could signify an attractive addition to the existing drug pipeline of Big Pharma. In this chapter, we will give an overview of the recent miRNA-based therapeutic approaches (patents: EP3110951, WO2017005771, EP3126496, EP3106168, WO2017005773, US9399773, EP2217248 and US9469854), and will discuss current translational challenges and further potential developments. These patents describe the potential of different miRNAs inhibitors/mimics for treating various types of cancers, these miRNAs include miR-34 mimic to treat hematologic malignancy/solid tumors; miR-409-5p, miR-379 and miR- 154 inhibitors to treat prostate cancer and drug resistant lung cancer; miR-548z, miR- 624-5p, let-7i-3p, miR-885-5p, miR-449b-3p to treat hepatoblastoma cancer; pre-miR- 302 (an miRNA precursor) for cancer reversion; miR-21, miR-125a-5p, miR-191, miR-210, miR-222, miR-378, miR-423-3p, miR-638 inhibitors to treat hepatocellular carcinoma (HCC); hsa-miR-4510, hsa-miR-548aa, hsa-miR- 548v and hsa-miR-37- b-3p mimics to treat HCC; sorafenib- miR- 34-mimic/ miR-215 mimic combination therapy for treating liver cancer and miR-21-3p mimic for treating liver diseases. The outcome of these patents may hopefully provide exciting opportunities and deeper insights into novel anti-cancer paradigms. Compared to conventional drug therapies, miRNA-based therapeutics appears to hold great promise to combat cancer, at least for those cancers where other treatment options have plateaued. Further developments in miRNA-based therapeutics are anticipated to translate miRNA-based therapeutic strategies into a clinical reality and may create a paradigm shift in medicine and pharmaceutical industry.

Keywords:

Anti-miR oligonucleotides, cancer, cancer therapy, cancerous cells, clinical trials, drug resistance, drug target, in vivo studies, miRNA inhibitor, miRNA masking, miRNA mimic, miRNAs sponges, miRNA therapeutics, mouse models, mRNAs, Non-coding RNAs, oncogenic miRNAs, pre-clinical trials, siRNAs, tumor suppressor miRNAs.

Affiliation:

Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), H-12 Islamabad, Pakistan.