Abstract
Simple SummaryNowadays, in clinics, there is a lack of reliable biomarkers that could serve as tools allowing for early cancer detection, prediction of therapy response, tumor recurrence, and TNBC course. In this review, we summarized the most recent findings on the applicability of unique blood circulating ncRNAs for management of TNBC. This review was supplemented by bioinformatics analysis for better understanding of molecular processes in which ncRNAs are involved, to promote individual TNBC phenotype and tumor action.Triple negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer, and is related to unfavorable prognosis and limited treatment strategies. Currently, there is a lack of reliable biomarkers allowing for the clinical management of TNBC. This is probably caused by a complex molecular background, leading to the development and establishment of a unique tumor phenotype. Recent studies have reported non-coding RNAs (ncRNAs) not only as the most promising class of molecular agents with a high applicability to manage human cancers, including TNBC, but also as robust and non-invasive biomarkers that are able to be monitored in blood circulation, with the application of liquid biopsy. There is a lack of papers discussing the role of blood-circulating ncRNAs as diagnostic, predictive, and prognostic biomarkers for TNBC. In this paper, we summarized the available literature reports on the utility of blood-circulating ncRNAs for TNBC management. Additionally, we supplemented this review by bioinformatics analysis, for better understanding of the role of ncRNAs’ machinery in the development of a unique TNBC phenotype.
Highlights
The above-described studies and performed bioinformatics analysis seem to confirm that combination of different classes of non-coding RNAs (ncRNAs) into diagnostic tests is a prospective direction for their clinical applicability, because they can represent key molecular pathways related to triple-negative breast cancer (TNBC) phenotype
Targeted treatment strategies for TNBC, including immunotherapy, will obviously require clinically useful biomarkers for therapy enrollment, monitoring, and prediction. ncRNAs are a promising group of biomarkers that can deal with the above-mentioned expectations, which seem to confirm recent in vitro studies made on pembrolizumab—a monoclonal antibody targeting plasma of docetaxel-resistant cases (PD)-1 that was approved for immunotherapy of locally recurrent unresectable/metastatic TNBC [97]. ncRNAs regulating the PD-1/PD-L1 axis are able to change the sensitivity of cells toward pembrolizumab
A regulatory network of miRNA–long non-coding RNA (lncRNA)–circular RNA (circRNA)–mRNA interactions demonstrates complex molecular machinery, in which each independent participant seems to be crucial for proper regulation of cell cycle and biological pathways
Summary
Despite the advances in diagnosis and implementation of adequate treatment options, including tailored targeted therapies, breast cancer (BC) is the second most common cause of cancer-related deaths in women worldwide [1,2]. According to the recent findings, the three of the most important players in the regulation of gene expression were identified in the ncRNAs family, as followed by microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA) [22,23] Their expression profiles can be used to discriminate between healthy and neoplastic states, as well as between different types of cancer [22,24]. RIanctetrioacntibonetbweteweenetnhtehetutummoorraanndd tthheehhoossttrerseuslutilntignign ianltearlatetiroantioofnncoRfNnAcRsNmAacshimnearcyhinery for for the development of the unique phenotype of TNBC and the usefulness of liquid biopsy for the the detvumeloorpmmaennagteomfetnhte—ualnteiqreudeexpphreesnsoiotnyppaettoerfnToNf nBcCRNaAnds dtrhiveeusasnefuunlfnaveosrsabolfelpiqheuniodtybpieopofscyanfocerr,the tumor manatghermefeonretp—roafilltienrgeodf necxRpNrAessiniobnloopdastatemrpnleorfefnlectRs NmoAlescudlarrivanedsacnlinuicnalfpaivctourraebolfeTNpBhCe.notype of cancer, profiling of ncRNAs in blood sample reflects molecular and clinical picture of TNBC. MiRNAs found to be related to TNBC were detected in blood circulation of patients suffering from other cancers (Figure 2A; Supplementary Table S1). miRNAs can serve as a potentially useful clinical screening tool, and their altered expression may be an introduction to more scrupulous diagnostics that allow earlier detection and treatment of cancer
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