<p>Resistance and Overcoming Resistance in Breast Cancer</p>

Abstract

The incidence and mortality of breast cancer (BC) have increased in recent years, and BC is the main cause of cancer-related death in women worldwide. One of the most significant clinical problems in the treatment of patients with BC is the development of therapeutic resistance. Therefore, elucidating the molecular mechanisms involved in drug resistance is critical. The therapeutic decision for the management of patients with BC is based not only on the assessment of prognostic factors but also on the evaluation of clinical and pathological parameters. Although this has been a successful approach, some patients relapse and/or eventually develop resistance to treatment. This review is focused on recent studies on the possible biological and molecular mechanisms involved in both response and resistance to treatment in BC. Additionally, emerging treatments that seek to overcome resistance and reduce side effects are also described. A greater understanding of the mechanisms of action of treatments used in BC might contribute not only to the enhancement of our understanding of the mechanisms involved in the development of resistance but also to the optimization of the existing treatment regimens.

MiR-21 Is Required for the Epithelial–Mesenchymal Transition in MDA-MB-231 Breast Cancer Cells

“…The resulting cDNA was used to assess the expression of miR-21, while RNU6 was used as a reference RNA for the normalization of miRNA expression levels. The relative expression of miR-21 was normalized with RNU6 expression levels using the comparative cycle threshold method [4]. The PerfeCTa SYBR Green SuperMix (Quantabio, Lutterworth, UK) was used together with MystiCq microRNA qPCR primers for miR-21 (hsa-miR-21-5p) obtained from Sigma (U.K.).…”

“…Treatment includes surgical intervention, radiotherapy (RT), systemic therapy with cytotoxic chemotherapy, hormone therapy, biological therapy, or a combination of all these therapies [3]. After breast-conserving surgery, the tumor bed represents the region with the highest recurrence (≤90%) [4]. In recent years, regular BCa screening measurements helped diagnose the tumors in more curable stages.…”

Zinc Signaling in the Mammary Gland: For Better and for Worse

“…Development of the normal breast is mostly regulated by estrogen acting through the ER [ 168 ], thereby controlling a variety of functions, including cell proliferation, angiogenesis, and apoptosis [ 66 ]. The ER signaling is used by breast cancer cells and, in the initial stages of the disease, serves as a major, estrogen-driven, survival pathway [ 168 , 169 , 170 ]. Therefore, expression of ER is used as a biomarker to guide therapy in breast cancer [ 171 ].…”

“…While this treatment is initially highly effective in attenuating growth, resistance of tumors to tamoxifen gradually develops usually in all patients, leading to intermittence and re-appearance of the disease [ 175 , 176 ]. Tamoxifen resistance may occur through modification of different signaling pathways involving growth factors such as EGF, IGF receptors, and the HER2 tyrosine kinase receptor [ 77 , 170 , 172 ]. Even though detection and treatment of metastatic breast cancer have advanced in recent years, the mortality caused by this disease remains high, due principally to such therapy-resistant breast cancer cells [ 169 , 177 , 178 ].…”

Genistein Mediated Molecular Pharmacology, Cell-Specific Anti-Breast Cancer Mechanism with Synergistic Effect and in silico Safety Measurement

“…Numerous drug molecules likely-anthracyclines (daunorubicin, doxorubicin, mitoxantrone, and epirubicin), taxanes (docetaxel, paclitaxel), and capecitabine were previously used successfully, but now these drugs are becoming resistant to cancer patients [7]. So, the modern medical emphasis is on preventing and treating breast cancer with natural nutritional components [8] [9] [10]. Under the pharmaceutical compoundsphytoestrogens are a natural dietary component with having potent anti-cancer activity against multiple cancer; most importantly, ovarian, prostate, as well as breast [11] [12].…”