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Abstract
Chemotherapy resistance remains an important problem in the breast cancer clinic. The ability to predict the patients who would respond to a distinct therapy would help to optimize tailored treatment options. miRNAs can mediate a number of genes in response to drug-induced acute cellular stress. Several studies suggest that let-7 miRNA may be involved in the chemosensitivity of cancer cell lines in vitro. However, it is not known whether this phenomenon occurs in clinical breast tumors. The present study showed that lower let-7a expression was associated with epirubicin resistance in primary breast tumors. Moreover, upregulation of let-7a expression sensitized resistant breast tumor cell lines to epirubicin by enhancing cellular apoptosis in vitro. Collectively, these findings indicate that lower expression of let-7a miRNA can induce chemoresistance in breast cancer by enhancing cellular apoptosis and suggest that let-7a may be used as a therapeutic target to modulate epirubicin-based chemotherapy resistance.
Highlights
Breast cancer is the most prevalent form of cancer in women worldwide, accounting for 23% of all female cancers [1]
The chemotherapeutic response was clinically evaluated by measuring the change in the tumor size in the breast as follows: (a) complete response (CR), disappearance of all known disease; (b) partial response (PR), 30% decrease in tumor size; (c) stable disease (SD),
We demonstrated that let-7 can regulate the self-renewal of breast tumor-initiating cells, and let-7 was rarely expressed in breast tumor-initiating cells, which are relatively resistant to epirubicin [10]
Summary
Breast cancer is the most prevalent form of cancer in women worldwide, accounting for 23% of all female cancers [1]. Neoadjuvant chemotherapy is the standard treatment for locally advanced breast cancer, which aims to improve the surgical options, achieve survival from disease and gain information on the tumor response [2]. Neoadjuvant chemotherapy improves patient survival, the disease outcomes remain dismal for those who do not achieve a complete pathological response after neoadjuvant chemotherapy [3,4,5,6]. Anthracycline-based neoadjuvant chemotherapy (doxorubicin or epirubicin) plays an important role in the neoadjuvant chemotherapy treatment of breast cancer. Not all of the patients benefit from the anthracycline–based neoadjuvant chemotherapy. Identifying the patients who can or cannot benefit from the anthracycline-based chemotherapy will have significant clinical implications in reducing the treatment cost and minimizing drug toxicity
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