Breast cancer: miRNAs monitoring chemoresistance and systemic therapy

Abstract

With a high mortality rate that accounts for millions of cancer-related deaths each year, breast cancer is the second most common malignancy in women. Chemotherapy has significant potential in the prevention and spreading of breast cancer; however, drug resistance often hinders therapy in breast cancer patients. The identification and the use of novel molecular biomarkers, which can predict response to chemotherapy, might lead to tailoring breast cancer treatment. In this context, accumulating research has reported microRNAs (miRNAs) as potential biomarkers for early cancer detection, and are conducive to designing a more specific treatment plan by helping analyze drug resistance and sensitivity in breast cancer treatment. In this review, miRNAs are discussed in two alternative ways-as tumor suppressors to be used in miRNA replacement therapy to reduce oncogenesis and as oncomirs to lessen the translation of the target miRNA. Different miRNAs like miR-638, miR-17, miR-20b, miR-342, miR-484, miR-21, miR-24, miR-27, miR-23 and miR-200 are involved in the regulation of chemoresistance through diverse genetic targets. For instance, tumor-suppressing miRNAs like miR-342, miR-16, miR-214, and miR-128 and tumor-promoting miRNAs like miR101 and miR-106-25 cluster regulate the cell cycle, apoptosis, epithelial to mesenchymal transition and other pathways to impart breast cancer drug resistance. Hence, in this review, we have discussed the significance of miRNA biomarkers that could assist in providing novel therapeutic targets to overcome potential chemotherapy resistance to systemic therapy and further facilitate the design of tailored therapy for enhanced efficacy against breast cancer.

The Discovery and Characterization of Conserved and Novel miRNAs in the Different Developmental Stages and Organs of Pikeperch (Sander lucioperca)

“…The clustered miRNAs 25, 93, and 106 also showed an increased expression of their mature miRNAs at this very early stage. This miRNA cluster is known to control the epithelial to mesenchymal transition in vertebrates [ 75 , 76 ]. Another miRNA gene cluster, 17-19-92, was significantly enriched at this very early stage.…”

Functions of Differentially Regulated miRNAs in Breast Cancer Progression: Potential Markers for Early Detection and Candidates for Therapy

“…To inhibit miRNA activity, small-molecule inhibitors specific to certain miRNAs are also being developed. The second strategy, miRNA replacement, includes the reintroduction of tumor-suppressor miRNA mimics to restore the loss of function [ 149 , 150 , 151 , 152 ].…”

“…miRNA inhibition therapy consists of the following agents: antisense anti-miRNA oligonucleotides (AMOs), LNA, antagomiRs, miRNA sponges, and miRNA small-molecule inhibitors (SMIRs) [ 155 ]. The fundamentals of these approaches are that endogenous miRNAs are isolated in an unrecognizable configuration, resulting in the inactivation and removal of mature miRNAs from the RISC [ 151 , 152 ]. Figure 2 shows the various miRNA inhibition therapies discussed here.…”

“…Synthetic miRNA mimics must be delivered efficiently for target cells for miRNA replacement therapy to be effective. There are a variety of delivery systems that can be used to ensure effective uptake by target tissues, including viral vectors, lipid nanoparticles, and other nanocarriers [ 150 , 151 , 152 , 170 ]. A synthetic miRNA mimic is incorporated into the RISC and acts similarly to endogenous miRNAs once inside a cell.…”

ASSESSMENT OF CIRCULATING miRNA LEVELS IN BREAST CANCER PATIENTS DEPENDING ON CLINICAL CHARACTERISTICS AND CHEMOTHERAPY

“…Breast cancer (BC) accounts for 6%-20% of all cancer-related mortality in women [1]. While the number of patients diagnosed with BC has been rising, the mortality rate has stabilized due to advancements in treatment [2].…”