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A B S T R A C TMetastatic breast cancer is a disease of early breast cancer that usually occurs several years after the early breast cancer. Breast cancer is the most common cancer among Iranian women. According to the new statistics in Iran 6160 breast cancers are diagnosed in the country each year and 1063 cases lead to death. In this paper, epidemiology, diagnosis and treatment have been investigated. In this study, case-control clinical trials and open studies with adequate data were collected. Due to the higher risk of age group 40-49 years and the advent of advanced breast cancer in Iranian women, the early diagnosis and determination of the exact size of the tumor before surgery is important in choosing a therapy plan. The decision on the therapy of invasive breast cancer depends on several factors such as cancer stage, tumor size and type, pathological and cytological status of the tumor, the patient's opinion, the presence or absence of estrogen and progesterone receptors in the cytoplasm of tumor cells and so on.

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The emergence of CRISPR/Cas technology has enabled scientists to precisely edit genomic DNA sequences. This approach can be used to modulate gene expression for the treatment of genetic disorders and incurable diseases such as cancer. This potent genome-editing tool is based on a single guide RNA (sgRNA) strand that recognizes the targeted DNA, plus a Cas nuclease protein for binding and processing the target. CRISPR/Cas has great potential for editing many genes in different types of cells and organisms both in vitro and in vivo. Despite these remarkable advances, the risk of off-target effects has hindered the translation of CRISPR/Cas technology into clinical applications. To overcome this hurdle, researchers have devised gene regulatory systems that can be controlled in a spatiotemporal manner, by designing special sgRNA, Cas, and CRISPR/Cas delivery vehicles that are responsive to different stimuli, such as temperature, light, magnetic fields, ultrasound (US), pH, redox, and enzymatic activity. These systems can even respond to dual or multiple stimuli simultaneously, thereby providing superior spatial and temporal control over CRISPR/Cas gene editing. Herein, we summarize the latest advances on smart sgRNA, Cas, and CRISPR/Cas nanocarriers, categorized according to their stimulus type (physical, chemical, or biological).