Abstract

Simple SummaryThe purpose of this systematic review was to assess the advancements in preclinical molecular imaging protocols used to study the delivery, tracking and therapeutic efficacy of miRNAs in mouse models of breast cancer. For this aim we have interrogated several browsers (PubMed, EMBASE, BIOSIS™ and Scopus) using the following terms: breast cancer, mouse, mice, microRNA(s) and miRNA(s). From 114 articles selected according to a PRISMA protocol, we focused on mouse models, routes of miRNA administration, therapy efficacy and molecular imaging. Importantly, we highlight here the advancements made in all imaging techniques’ applications used, providing a useful tool, on the basis of the current evidence, with which to suggest the best preclinical imaging protocol.Background: We have conducted a systematic review focusing on the advancements in preclinical molecular imaging to study the delivery and therapeutic efficacy of miRNAs in mouse models of breast cancer. Methods: A systematic review of English articles published in peer-reviewed journals using PubMed, EMBASE, BIOSIS™ and Scopus was performed. Search terms included breast cancer, mouse, mice, microRNA(s) and miRNA(s). Results: From a total of 2073 records, our final data extraction was from 114 manuscripts. The most frequently used murine genetic background was Balb/C (46.7%). The most frequently used model was the IV metastatic model (46.8%), which was obtained via intravenous injection (68.9%) in the tail vein. Bioluminescence was the most used frequently used tool (64%), and was used as a surrogate for tumor growth for efficacy treatment or for the evaluation of tumorigenicity in miRNA-transfected cells (29.9%); for tracking, evaluation of engraftment and for response to therapy in metastatic models (50.6%). Conclusions: This review provides a systematic and focused analysis of all the information available and related to the imaging protocols with which to test miRNA therapy in an in vivo mice model of breast cancer, and has the purpose of providing an important tool to suggest the best preclinical imaging protocol based on available evidence.

Highlights

  • As has been recently estimated, breast cancer (BC) alone accounts for ~30% of all new diagnoses in women [1]

  • Reviews were searched for other relevant references, but no other eligible papers were detected. In this phase 852 records were excluded and 1221 papers were assessed for full text eligibility, excluding all those in which there was no use of mouse models of BC, there was not in vivo imaging or ex vivo on whole organs, i.e., were excluded imaging techniques applied to histological samples

  • Regarding the effects of miRNA delivery on either tumor growth or lung metastasis, we found that luciferase expressing BC cells transfected with miR-101 [25], -141 [116], -361-5p [56], -30a-5p [127], -125a-5p [73], -1 [91], -211-5p [128], -190 [79], -206 [95], -33b [23], -33a [120], -96 [22], -133b [54], -1 [70], -494 [78], -29b/-30d [30], anti-miR-1204 [53] and miR-191/-425 sponge [43] exerted antitumor and metastatic activity compared to BC cells transfected with an empty vector

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Summary

Introduction

As has been recently estimated, breast cancer (BC) alone accounts for ~30% of all new diagnoses in women [1]. Improvements in BC’s early diagnostic strategies and therapy have increased survival rates, this malignant tumor remains one of the most frequent causes of cancer-related mortality among females worldwide [1]. To date, it is well-known that BC is a complex and heterogeneous disease that can be classified into several subtypes based on histological and genetic characteristics. Conclusions: This review provides a systematic and focused analysis of all the information available and related to the imaging protocols with which to test miRNA therapy in an in vivo mice model of breast cancer, and has the purpose of providing an important tool to suggest the best preclinical imaging protocol based on available evidence. As it Beige CB17.Cg-PrkdcscidHrhr/IcrCrl -Prkdcem I/2rgem26 /Nju As it NOD.CB17-Prdkcscid/J B6.CB17-Prkdcscid/Sz

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