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Triple-negative breast cancer (TNBC) is the most aggressive and prevalent subtype of breast cancer in women worldwide. Currently, chemotherapy remains the main modality for the treatment at an early stage, as there is no approved targeted therapy for early TNBC. In this review, we investigate the use of microRNAs (miRNAs), which play a key role in the post-transcriptional regulation of genes involved in the key biological processes, namely proliferation, differentiation, angiogenesis, migration, apoptosis, and carcinogenesis. Here, we emphasize the importance of the recent advances related to miRNAs, involving diagnosis, prognosis, and treatment of TNBC. We focus on the development, optimization, and stabilization of miRNA-based drugs; improvement of miRNA delivery; and control of the off-target effects of miRNA therapeutics. We speculate as to which features may present themselves as promising approaches in the treatment of TNBC. Keywords TNBC. miRNA. Cancer biomarkers. miRNA-based therapy Abbreviations Bmi 1 B lymphoma Mo-MLV insertion region 1 homolog CSC Cancer stem cells ER Estrogen receptor HER 2 Human epidermal growth factor receptor 2 PR Progesterone receptor TNBC Triple-negative breast cancer ts-microRNA Tumor suppressor microRNA Highlights • Patients diagnosed with negative ER, PR, and HER 2 are the most prevalent subtypes of breast cancer with limited targeted therapy. • miRNAs play a key role in regulating the gene expression of the key biological processes including proliferation, differentiation, angiogenesis, migration, and apoptosis. The involvement of miRNA has also been identified in carcinogenesis. • In TNBC, miRNAs make major contributions to the diagnosis, prognosis, and treatment. • We suggest that miRNA-based therapeutics could be a promising approach in the treatment of TNBC.

Background: The potential of Super Paramagnetic Iron Oxide Nanoparticles (SPIONs) as theranostic agents for cancer has been investigated extensively. SPIONS can be utilized for diagnostic imaging, drug delivery as well as for therapeutic applications. SPIONS are of particular interest because of their potential for non-invasive diagnosis and non-invasive therapeutic applications. This article is a review of in vivo and clinical studies of SPIONs for diagnosis and treatment of breast, ovarian and cervical cancer. The current limitations of this technology with relation to clinical therapeutic applications and the potential to overcome these limitations are also discussed. Methods: NCBI Pubmed was searched for relevant documents by using keyword and MESH based search. The following keyword combinations were used: ‘breast cancer’ and SPION, ‘ovarian cancer’ and SPION, and ‘cervical cancer’ and SPION. The resulting list was manually scanned for the studies involving clinical and in vivo studies. Results: The 29 most relevant publications were identified and reviewed. Conclusion: Although numerous in vitro and in vivo studies have demonstrated the safety and effectiveness of the use of SPIONs for both diagnostic and therapeutic applications, there is relatively little progress towards translation to clinical applications involving breast, ovarian and cervical cancer.

Cluster of differentiation 151 (CD151) is a member of the mammalian tetraspanin family, which is involved in diverse functions such as maintaining normal cellular integrity, cell-to-cell communication, wound healing, platelet aggregation, trafficking, cell motility and angiogenesis. CD151 also supports de novo carcinogenesis in human skin squamous cell carcinoma (SCC) and tumor metastasis. CD151 interacts with α3β1 and α6β4 integrins through palmitoylation where cysteine plays an important role in the association of CD151 with integrins and non-integrin proteins. Invasion and metastasis of cancer cells were diminished by decreasing CD151 association with integrins. CD151 functions at various stages of cancer, including metastatic cascade and primary tumor growth, thus reinforcing the importance of CD151 as a target in oncology. The present review highlights the role of CD151 in tumor metastasis and its importance in cancer therapy.

Triple‐negative breast cancer (TNBC) is an aggressive and immunogenic subtype of breast cancer. This tumorigenicity is independent of hormonal or HER2 pathways because of a lack of respective receptor expression. TNBC is extremely prone to drug resistance and early recurrence because of T‐regulatory cell (Treg) infiltration into the tumor microenvironment (TME) in addition to other mechanisms like genomic instability. Tumor‐infiltrating Tregs interact with both tumor and stromal cells as well as extracellular matrix components in the TME and induce an immune‐suppressive phenotype. Hence, treatment of TNBC with conventional therapies remains challenging. Understanding the protective mechanism of Tregs in shielding TNBC from antitumor immune responses in the TME will pave the way for developing novel, immune‐based therapeutics. The current review focuses on the role of tumor‐infiltrating Tregs in tumor progression and metabolic reprogramming of the TME. The authors have extended their focus to oncotargeting Treg‐mediated immune suppression in breast cancer. Because of its potential role in the TME, modulating Treg activity may provide a novel strategic intervention to combat TNBC. Both under laboratory conditions and in clinical trials, currently available anticancer drugs and natural therapeutics as potential agents for targeting Tregs are explored.

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HOX transcript antisense intergenic RNA (HOTAIR) is an oncogenic non-coding RNA whose expression is strongly correlated with the tumor grade and prognosis of a variety of carcinomas including breast cancer (BC). HOTAIR regulates various target genes via sponging and epigenetic mechanisms and controls various oncogenic cellular and signaling mechanisms including metastasis and drug resistance. In BC cells, HOTAIR expression is regulated by a variety of transcriptional and epigenetic mechanisms. In this review, we describe the regulatory mechanisms that govern HOTAIR expression during cancer development and explore how HOTAIR drives BC development, metastasis, and drug resistance. In the final section of this review, we focus on the role of HOTAIR in BC management, therapeutic treatment, and prognosis, highlighting its potential therapeutic applications.