miRNAs in anti-cancer drug resistance of non-small cell lung cancer: Recent advances and future potential

Abstract

Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors worldwide. Clinical success is suboptimal owing to late diagnosis, limited treatment options, high recurrence rates, and the development of drug resistance. MicroRNAs (miRNAs), a range of small endogenous non-coding RNAs that are 22 nucleotides in length, have emerged as one of the most important players in cancer initiation and progression in recent decades. Current evidence has revealed the pivotal roles of miRNAs in regulating cell proliferation, migration, invasion, and metastasis in NSCLC. Recently, several studies have demonstrated that miRNAs are strongly associated with resistance to anti-cancer drugs, ranging from traditional chemotherapeutic and immunotherapy drugs to anti-vascular drugs, and even during radiotherapy. In this review, we briefly introduce the mechanism of miRNA dysregulation and resistance to anti-tumor therapy in NSCLC, and summarize the role of miRNAs in the malignant process of NSCLC. We then discuss studies of resistance-related miRNAs in chemotherapy, radiotherapy, targeted therapy, immunotherapy, and anti-vascular therapy in NSCLC. Finally, we will explore the application prospects of miRNA, an emerging small molecule, for future anti-tumor therapy. This review is the first to summarize the latest research progress on miRNAs in anti-cancer drug resistance based on drug classification, and to discuss their potential clinical applications.

Monitoring EGFR-lung cancer evolution: a possible beginning of a “methylation era” in TKI resistance prediction

“…The deregulation of miRNA machinery is linked to the acquisition of cancer hallmarks that lead to genome instability and impact on tumor growth, invasion and metastatization ( 82 ). Recent findings have shown that miRNAs could modulate as post-transcriptional regulators the response to EGFR TKIs in overcoming resistance in NSCLC patients, as summarized in Table 2 ( 92 , 93 ). The first evidence of this derived from Hashida S and colleagues’ work, whom investigated the EGFR-TKI resistance mechanisms in a total of 10 afatinib-resistant cell lines from parental NSCLC cells with activating EGFR mutations ( 83 ).…”

Non-Coding RNAs as Key Regulators in Lung Cancer

“…The first-generation EGFR-TKIs, such as gefitinib and erlotinib, play a crucial role in the management of LC. However, it is imperative to acknowledge the emergence of resistance to these agents [ 73 ]. Numerous studies have demonstrated the involvement of miRNAs in the development of this resistance.…”

“…In particular, immunotherapy employing anti-PD-1 or anti-PD-L1 antibodies has emerged as a prominent therapeutic approach for individuals afflicted with advanced NSCLC and SCLC [ 83 , 84 , 85 , 86 ]. In spite of notable clinical advancements, a majority of patients experience suboptimal responses to ICI therapy due to the emergence of primary or secondary resistance [ 73 ].…”

A dynamic Boolean network reveals that the BMI1 and MALAT1 axis is associated with drug resistance by limiting miR-145-5p in non-small cell lung cancer

“…LncRNAs have a variety of roles in biology, including cell-cycle progression, apoptosis, and genomic stability [ 6 ]. Similarly, miRNAs, which typically range from 19 to 25 nucleotides in size, play various roles in biological systems, including their involvement in tumor formation [ 7 ].…”