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MiRNA-Based Therapeutics in Breast Cancer: A Systematic Review.

ABSTRACT:

Background

Breast cancer (BC) is the most common cancer in females and despite advances in treatment, it represents the leading cause of cancer mortality in women worldwide. Conventional therapeutic modalities have significantly improved the management of BC patients, but subtype heterogeneity, drug resistance, and tumor relapse remain the major factors to hamper the effectiveness of therapy for BC. In this scenario, miRNA(miR)-based therapeutics offer a very attractive area of study. However, the use of miR-based therapeutics for BC treatment still represents an underdeveloped topic. Therefore, this systematic review aims at summarizing current knowledge on promising miR-based therapeutics for BC exploring original articles focusing on in vivo experiments.

Methods

The current systematic review was performed according to PRISMA guidelines. PubMed and EMBASE databases were comprehensively explored to perform the article search.

Results

Twenty-one eligible studies were included and analyzed: twelve focused on antitumor miR-based therapeutics and nine on metastatic miR-based therapeutics. We found 18 different miRs tested as potential therapeutic molecules in animal model experiments. About 90% of the selected studies evaluate the efficiency and the safety of miRs as therapeutic agents in triple-negative (TN)-BC mouse models. Among all founded miR-based therapeutics, miR-21 emerged to be the most investigated and proposed as a potential antitumoral molecule for TNBC treatment. Besides, miR-34a and miR-205a appeared to be successful antitumoral and antimetastatic molecules.

Conclusions

Our analysis provides a snapshot of the current scenario regarding the miRs as therapeutic molecules in BC. Nevertheless, despite many efforts, none of the selected studies goes beyond preclinical studies, and their translatability in the clinical practice seems quite premature.

SUBMITTER: Grimaldi AM

PROVIDER: S-EPMC8131824 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Multiple studies have investigated global DNA methylation profiles and gene-specific DNA methylation in blood-based DNA to develop powerful screening markers for cancer. This systematic review summarizes the current evidence on methylation studies that investigated methylation level of blood-derived DNA of breast cancer (BC) patients in comparison to healthy controls by conducting a systematic literature review in PubMed and Web of Science. Essential results, such as methylation levels of BC cases and healthy controls, p values, and odds ratios, were extracted from these studies by two investigators independently. Overall, 45 publications met the inclusion criteria for this review. DNA from whole blood, as well as cell-free DNA (cfDNA) from serum or plasma, was used in these studies. The most common method used for measuring global DNA methylation was the investigation of repetitive elements as surrogates and the application of array-based genome-wide methylation analysis. For measuring gene-specific methylation level, methylation-specific PCR and pyrosequencing were the most frequently used methods. Epigenome-wide blood DNA hypomethylation in BC patients were reported in several studies; however, the evidence is still not conclusive. The most frequently investigated gene in whole blood was BRCA1, which was found more frequently methylated in patients compared to controls. RASSF1A was the most widely investigated gene in cfDNA of serum or plasma, which was also found more frequently methylated in patients compared to controls. Several of the eligible studies reported the associations of global hypomethylation and increased BC risk. Studies investigated associations between gene-specific methylation and BC risk, while got heterogeneous results. But two studies reported that hypermethylation of ATM gene was associated with increased BC risk, which suggest the potential use of this gene for BC risk stratification. Overall, our review suggests the possibility of using blood-based DNA methylation marker as promising marker for BC risk stratification, as several studies found associations between certain methylation level in blood and BC risk. However, so far, the evidence is still quite limited. Optimal markers are yet to be developed and promising results needed to be validated in prospective study cohorts and tested in large screening populations.