The Small RNA Landscape in NSCLC: Current Therapeutic Applications and Progresses

Abstract

Non-small-cell lung cancer (NSCLC) is the second most diagnosed type of malignancy and the first cause of cancer death worldwide. Despite recent advances, the treatment of choice for NSCLC patients remains to be chemotherapy, often showing very limited effectiveness with the frequent occurrence of drug-resistant phenotype and the lack of selectivity for tumor cells. Therefore, new effective and targeted therapeutics are needed. In this context, short RNA-based therapeutics, including Antisense Oligonucleotides (ASOs), microRNAs (miRNAs), short interfering (siRNA) and aptamers, represent a promising class of molecules. ASOs, miRNAs and siRNAs act by targeting and inhibiting specific mRNAs, thus showing an improved specificity compared to traditional anti-cancer drugs. Nucleic acid aptamers target and inhibit specific cancer-associated proteins, such as “nucleic acid antibodies”. Aptamers are also able of receptor-mediated cell internalization, and therefore, they can be used as carriers of secondary agents giving the possibility of producing very highly specific and effective therapeutics. This review provides an overview of the proposed applications of small RNAs for NSCLC treatment, highlighting their advantageous features and recent advancements in the field.

Nature’s carriers: leveraging extracellular vesicles for targeted drug delivery

“…The therapeutic efficacy is unsatisfactory. There are various reasons, for instance, due to their short half-life, immunogenicity, failure to pass the blood-brain barrier, off-target effects and so on (Castanotto & Rossi, 2009 ; Ciccone et al., 2023 ). To improve targeting ability and good biocompatibility, EVs from breast cancer cells were used to load sis100A4 (Zhao et al., 2020 ; Pan et al., 2023 ).…”

Advances in Nucleic Acid Research: Exploring the Potential of Oligonucleotides for Therapeutic Applications and Biological Studies

“…ASOs have been widely employed in nonsmall cell lung cancer (NSCLC) therapy to target key gene regulators involved in the malignant phenotype. Some of the targeted genes include Bcl2 , protein kinase B , Kirsten rat sarcoma virus ( KRAS ), vascular endothelial growth factor , signal transducer and activator of transcription 3 , clusterin , and protein kinase C alpha ( PKC alpha ) [ 62 ]. Currently, aprinocarsen (NCT00017407, NCT0034268) and custirsen (NCT01630733, NCT00138658) are under clinical trials targeting PKC alpha and clusterin , respectively, which are associated with NSCLC.…”

Aptamers’ Potential to Fill Therapeutic and Diagnostic Gaps

“…Cancer, in its broadest sense, attracts a great deal of interest and many resources, and aptamer technology is no stranger to this. Cancer treatment has also been the focus of many aptamer-based studies [ 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. However, other diseases such as neurodegenerative or cardiovascular diseases, among others, have also been targeted in aptamer studies [ 47 , 48 , 49 , 50 , 51 , 52 ].…”