Drug resistance is a daunting challenge in the treatment of breast cancer (BC). Exosomes, as intercellular communicative vectors in the tumor microenvironment, play an important role in BC progression. With the in-depth understanding of tumor heterogeneity, an emerging role of exosomes in drug resistance has attracted extensive attention. The functional proteins or non-coding RNAs contained in exosomes secreted from tumor and stromal cells mediate drug resistance by regulating drug efflux and metabolism, pro-survival signaling, epithelial–mesenchymal transition, stem-like property, and tumor microenvironmental remodeling. In this review, we summarize the underlying associations between exosomes and drug resistance of BC and discuss the unique biogenesis of exosomes, the change of exosome cargo, and the pattern of release by BC cells in response to drug treatment. Moreover, we propose exosome as a candidate biomarker in predicting and monitoring the therapeutic drug response of BC and as a potential target or carrier to reverse the drug resistance of BC.

/pdf/exosomes-and-breast-cancer-drug-resistance-4bgkcgjrlo.pdf

Exosomes and breast cancer drug resistance.

Current cancer therapies, including chemotherapy and radiotherapy, are imprecise, non-specific, and are often administered at high dosages - resulting in side effects that severely impact the patient's overall well-being. A variety of multifunctional, cancer-targeted nanotheranostic systems that integrate therapy, imaging, and tumor targeting functionalities in a single platform have been developed to overcome the shortcomings of traditional drugs. Among the imaging modalities used, magnetic resonance imaging (MRI) provides high resolution imaging of structures deep within the body and, in combination with other imaging modalities, provides complementary diagnostic information for more accurate identification of tumor characteristics and precise guidance of anti-cancer therapy. This review article presents a comprehensive assessment of nanotheranostic systems that combine MRI-based imaging (T1 MRI, T2 MRI, and multimodal imaging) with therapy (chemo-, thermal-, gene- and combination therapy), connecting a range of topics including hybrid treatment options (e.g. combined chemo-gene therapy), unique MRI-based imaging (e.g. combined T1-T2 imaging, triple and quadruple multimodal imaging), novel targeting strategies (e.g. dual magnetic-active targeting and nanoparticles carrying multiple ligands), and tumor microenvironment-responsive drug release (e.g. redox and pH-responsive nanomaterials). With a special focus on systems that have been tested in vivo, this review is an essential summary of the most advanced developments in this rapidly evolving field.

MRI-traceable theranostic nanoparticles for targeted cancer treatment

MicroRNAs (miRNAs) are non-coding RNAs with a length of 18–22 nucleotides that regulate about a third of the human genome at the post-transcriptional level. MiRNAs are involved in almost all biological processes, including cell proliferation, apoptosis, and cell differentiation, but also play a key role in the pathogenesis of many diseases. Most miRNAs are expressed within the cells themselves. Due to various forms of transport from cells like exosomes, circulating miRNAs are stable and can be found in human body fluids, such as blood, saliva, cerebrospinal fluid, and urine. Circulating miRNAs are of great interest as potential noninvasive biomarkers for tumors, lipid disorders, diabetes mellitus, and cardiovascular diseases. However, the possibility of their use in the clinic is limited, and this is associated with a number of problems since currently there are significant differences between the procedures for processing samples, methods of analysis, and especially strategies for standardizing results. Moreover, miRNAs can represent not only potential biomarkers but also become new therapeutic agents and be used in modern clinical practice, which again confirms the need for their study.

The current state of MiRNAs as biomarkers and therapeutic tools.

Breast cancer is the most commonly diagnosed cancer type and the leading cause of cancer-related mortality in women worldwide. Breast cancer is fairly heterogeneous and reveals six molecular subtypes: luminal A, luminal B, HER2+, basal-like subtype (ER−, PR−, and HER2−), normal breast-like, and claudin-low. Breast cancer screening and early diagnosis play critical roles in improving therapeutic outcomes and prognosis. Mammography is currently the main commercially available detection method for breast cancer; however, it has numerous limitations. Therefore, reliable noninvasive diagnostic and prognostic biomarkers are required. Biomarkers used in cancer range from macromolecules, such as DNA, RNA, and proteins, to whole cells. Biomarkers for cancer risk, diagnosis, proliferation, metastasis, drug resistance, and prognosis have been identified in breast cancer. In addition, there is currently a greater demand for personalized or precise treatments; moreover, the identification of novel biomarkers to further the development of new drugs is urgently needed. In this review, we summarize and focus on the recent discoveries of promising macromolecules and cell-based biomarkers for the diagnosis and prognosis of breast cancer and provide implications for therapeutic strategies.

https://www.mdpi.com/1422-0067/22/2/636/pdf

Recent Discoveries of Macromolecule- and Cell-Based Biomarkers and Therapeutic Implications in Breast Cancer.

Breast cancer is the second most reported cancer in women with high mortality causing millions of cancer-related deaths annually. Early detection of breast cancer intensifies the struggle towards discovering, developing, and optimizing diagnostic biomarkers that can improve its prognosis and therapeutic outcomes. Breast cancer-associated biomarkers comprise macromolecules, such as nucleic acid (DNA/RNA), proteins, and intact cells. Advancements in molecular technologies have identified all types of biomarkers that are exclusively studied for diagnostic, prognostic, drug resistance, and therapeutic implications. Identifying biomarkers may solve the problem of drug resistance which is a challenging obstacle in breast cancer treatment. Dysregulation of non-coding RNAs including circular RNAs (circRNAs) and microRNAs (miRNAs) initiates and progresses breast cancer. The circulating multiple miRNA profiles promise better diagnostic and prognostic performance and sensitivity than individual miRNAs. The high stability and existence of circRNAs in body fluids make them a promising new diagnostic biomarker. Many therapeutic-based novels targeting agents have been identified, including ESR1 mutation (DNA mutations), Oligonucleotide analogs and antagonists (miRNA), poly (ADP-ribose) polymerase (PARP) in BRCA mutations, CDK4/6 (cell cycle regulating factor initiates tumor progression), Androgen receptor (a steroid hormone receptor), that have entered clinical validation procedure. In this review, we summarize the role of novel breast cancer diagnostic biomarkers, drug resistance, and therapeutic implications for breast cancer.

/pdf/breast-cancer-discovery-of-novel-diagnostic-biomarkers-drug-2kiwtjcs.pdf

Breast Cancer; Discovery of Novel Diagnostic Biomarkers, Drug Resistance, and Therapeutic Implications

Awareness of breast cancer has been increasing due to early detection, but the advanced disease has limited treatment options. There has been growing evidence on the role of miRNAs involved in regulating the resistance in several cancers. We performed a comprehensive systematic review and meta-analysis on the role of miRNAs in influencing the chemoresistance and sensitivity of breast cancer. A bibliographic search was performed in PubMed and Science Direct based on the search strategy, and studies published until December 2018 were retrieved. The eligible studies were included based on the selection criteria, and a detailed systematic review and meta-analysis were performed based on PRISMA guidelines. A random-effects model was utilised to evaluate the combined effect size of the obtained hazard ratio and 95% confidence intervals from the eligible studies. Publication bias was assessed with Cochran's Q test, I2 statistic, Orwin and Classic fail-safe N test, Begg and Mazumdar rank correlation test, Duval and Tweedie trim and fill calculation and the Egger's bias indicator. A total of 4584 potential studies were screened. Of these, 85 articles were eligible for our systematic review and meta-analysis. In the 85 studies, 188 different miRNAs were studied, of which 96 were upregulated, 87 were downregulated and 5 were not involved in regulation. Overall, 24 drugs were used for treatment, with doxorubicin being prominently reported in 15 studies followed by Paclitaxel in 11 studies, and 5 drugs were used in combinations. We found only two significant HR values from the studies (miR-125b and miR-4443) and our meta-analysis results yielded a combined HR value of 0.748 with a 95% confidence interval of 0.508-1.100; p-value of 0.140. In conclusion, our results suggest there are different miRNAs involved in the regulation of chemoresistance through diverse drug genetic targets. These biomarkers play a crucial role in guiding the effective diagnostic and prognostic efficiency of breast cancer. The screening of miRNAs as a theragnostic biomarker must be brought into regular practice for all diseases. We anticipate that our study serves as a reference in framing future studies and clinical trials for utilising miRNAs and their respective drug targets.

https://www.mdpi.com/2073-4409/8/10/1250/pdf

Clinical Theragnostic Relationship between Drug-Resistance Specific miRNA Expressions, Chemotherapeutic Resistance, and Sensitivity in Breast Cancer: A Systematic Review and Meta-Analysis

Shubhangi Sathyakumar

Papers

Clinical Theragnostic Relationship between Drug-Resistance Specific miRNA Expressions, Chemotherapeutic Resistance, and Sensitivity in Breast Cancer: A Systematic Review and Meta-Analysis

The Parkinson’s disease protein alpha-synuclein is a modulator of processing bodies and mRNA stability