Abstract
Breast cancer, specifically metastatic breast, is a leading cause of morbidity and mortality in women. This is mainly due to relapse and reoccurrence of tumor. The primary reason for cancer relapse is the development of multidrug resistance (MDR) hampering the treatment and prognosis. MDR can occur due to a multitude of molecular events, including increased expression of efflux transporters such as P-gp, BCRP, or MRP1; epithelial to mesenchymal transition; and resistance development in breast cancer stem cells. Excessive dose dumping in chemotherapy can cause intrinsic anti-cancer MDR to appear prior to chemotherapy and after the treatment. Hence, novel targeted nanomedicines encapsulating chemotherapeutics and gene therapy products may assist to overcome cancer drug resistance. Targeted nanomedicines offer innovative strategies to overcome the limitations of conventional chemotherapy while permitting enhanced selectivity to cancer cells. Targeted nanotheranostics permit targeted drug release, precise breast cancer diagnosis, and importantly, the ability to overcome MDR. The article discusses various nanomedicines designed to selectively target breast cancer, triple negative breast cancer, and breast cancer stem cells. In addition, the review discusses recent approaches, including combination nanoparticles (NPs), theranostic NPs, and stimuli sensitive or “smart” NPs. Recent innovations in microRNA NPs and personalized medicine NPs are also discussed. Future perspective research for complex targeted and multi-stage responsive nanomedicines for metastatic breast cancer is discussed.
Highlights
Breast Cancer ClassificationBreast cancer treatment is divided into two treatment options. This includes regional treatment and systemic therapy
Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, MO 64108, USA; Department of Biomedical Engineering, College of Engineering, The University of Texas at El Paso, Department of Basic Pharmaceutical Sciences, Fred Wilson School of Pharmacy, High Point University, High Point, NC 27268, USA
Efflux transporters mainly include: (i) P-gp, an ABC sub-family-B member-1 encoded in the human body by ABCB1 gene; (ii) Breast cancer resistance protein (BCRP), a member of the white sub-family and ABCG member 2 encoded in the human body by the ABCG2 gene; and (iii) multidrug resistance associated protein-1 (MRP-1), an ATP-binding cassette sub-family C member 2 encoded in the human body by the ABCC2 gene [23,24]
Summary
Breast cancer treatment is divided into two treatment options. This includes regional treatment and systemic therapy. The surrogate classification of breast cancer is commonly used This classification includes five types of breast cancers classified according to varying molecular and histological differences in breast cancer (Figure 1). This intrinsic classification shifted clinical management of the disease from being based on tumor biology to a molecular targeted approach. Another way of classifying breast cancer is by the presence and absence of receptors on the cell surface. Triple negative breast cancer (TNBC) lacks the expression of ER, PR, and HER2 This type of breast cancer cannot be treated with hormone therapy or HER2 targeted therapy. Chemotherapy is the only current option for the treatment of TNBC [2]
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