Abstract

Lung cancer is one of the most commonly diagnosed cancers and is responsible for a large number of deaths worldwide. The pathogenic mechanism of lung cancer is complex and multifactorial in origin. Thus, various signaling pathways as targets for therapy are being examined, and many new drugs are in the pipeline. However, both conventional and target-based drugs have been reported to present significant adverse effects, and both types of drugs can affect the clinical outcome in addition to patient quality of life. Recently, miRNA has been identified as a promising target for lung cancer treatment. Therefore, miRNA mimics, oncomiRs, or miRNA suppressors have been developed and studied for possible anticancer effects. However, these miRNAs also suffer from the limitations of low stability, biodegradation, thermal instability, and other issues. Thus, nanocarrier-based drug delivery for the chemotherapeutic drug delivery in addition to miRNA-based systems have been developed so that existing limitations can be resolved, and enhanced therapeutic outcomes can be achieved. Thus, this review discusses lung cancer’s molecular mechanism, currently approved drugs, and their adverse effects. We also discuss miRNA biosynthesis and pathogenetic role, highlight pre-clinical and clinical evidence for use of miRNA in cancer therapy, and discussed limitations of this therapy. Furthermore, nanocarrier-based drug delivery systems to deliver chemotherapeutic drugs and miRNAs are described in detail. In brief, the present review describes the mechanism and up-to-date possible therapeutic approaches for lung cancer treatment and emphasizes future prospects to bring these novel approaches from bench to bedside.

Highlights

  • According to World Health Organization (WHO), lung cancer (LC) is a major cause of death and is the second most commonly diagnosed cancer worldwide

  • Involvement of miRNA in pathogenesis has been well established, and it was found that the factors that affect the biosynthesis of miRNA at the pri- or pre-miRNA level are primarily responsible for causing dysregulated miRNA and carcinogenesis [100]

  • The outcome of this study showed an increase in apoptosis and a reduction in tumor growth [134]. miR-154 in combination with cisplatin encapsulated in

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Summary

A Review

Alhakamy 1,2,3 , Shahid Karim 4 , Gamal A Gabr 5 , Mohammad Kashif Iqubal 6,7 and Samar S. Inhibitors, miRNA, and NanocarrierBased Pharmacotherapeutics for the Treatment of Lung Cancer: A Review. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Sentiss Research Centre, Product Development Department, Sentiss Pharma Pvt Ltd., Gurugram 122001, India

Introduction
Signaling Pathways and Targeted Therapy in LC
Limitations of the Approved and Pipeline Drugs of Lungs Cancer
Nanocarrier-Based Targeted Drug Delivery in LC
Polymeric Nanoparticles
Liposome
Nanoemulsion
Polymeric Micelle
The Limitations of Nanocarrier Drug Delivery Systems and miRNA as Emerging
Mechanism of miRNA Deregulation in Lung Cancer
Preclinical Based Evidence of miRNA in Lung Cancer
Translatory and Clinical-Based Evidence of miRNA in Lung Cancer
Challenges in Developing miRNA-Based Therapeutics
Findings
Conclusions and Future Prospects
Full Text
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