MicroRNA-targeted therapeutics for lung cancer treatment

ABSTRACT

Introduction: Lung cancer is one of the leading causes of cancer-related mortality worldwide. MicroRNAs (miRNAs) are endogenous non-coding small RNAs that repress the expression of a broad array of target genes. Many efforts have been made to therapeutically target miRNAs in cancer treatments using miRNA mimics and miRNA antagonists.

Areas covered: This article summarizes the recent findings with the role of miRNAs in lung cancer, and discusses the potential and challenges of developing miRNA-targeted therapeutics in this dreadful disease.

Expert opinion: The development of miRNA-targeted therapeutics has become an important anti-cancer strategy. Results from both preclinical and clinical trials of microRNA replacement therapy have shown some promise in cancer treatment. However, some obstacles, including drug delivery, specificity, off-target effect, toxicity mediation, immunological activation and dosage determination should be addressed. Several delivery strategies have been employed, including naked oligonucleotides, liposomes, aptamer-conjugates, nanoparticles and viral vectors. However, delivery remains a main challenge in miRNA-targeting therapeutics. Furthermore, immune-related serious adverse events are also a concern, which indicates the complexity of miRNA-based therapy in clinical settings.

KEYWORDS:

• Delivery system
• EGFR
• lung cancer
• MicroRNA
• off-target
• therapeutic target

Article highlights

• Dysregulated microRNA (miRNA) expressions are found in lung cancer cells and tissues.

• Strategies to manipulate miRNA activity including tools for miRNA inhibition (e.g. antisense oligonucleotides, miRNA sponges and tough decoys) or miRNA replacement (e.g. mimics) have been developed.

• Several miRNA-based therapies have been explored in the preclinical studies of lung cancer with encouraged results.

• The translational efficacy and safety of miR-34 mimic for patients with lung cancer has been reported in clinical trials.

• miRNA-targeting therapeutics may aid in developing novel agents and strategies for lung cancer treatment.

• Challenges of miRNA-targeting therapeutics for lung cancer include the mode of delivery, targeted specificity and potential off-target effects, toxicity and dosage, as well as immunological activation.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China under Grant [Number 31472191].