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Most breast cancers at an advanced stage exhibit an aggressive nature, and there is a lack of effective anticancer options. Herein, the development of patient-derived organoids (PDOs) is described as a real-time platform to explore the feasibility of tailored treatment for refractory breast cancers. PDOs are successfully generated from breast cancer tissues, including heavily treated specimens. The microtubule-targeting drug-sensitive response signatures of PDOs predict improved distant relapse-free survival for invasive breast cancers treated with adjuvant chemotherapy. It is further demonstrated that PDO pharmaco-phenotyping reflects the previous treatment responses of the corresponding patients. Finally, as clinical case studies, all patients who receive at least one drug predicate to be sensitive by PDOs achieve good responses. Altogether, the PDO model is developed as an effective platform for evaluating patient-specific drug sensitivity in vitro, which can guide personal treatment decisions for breast cancer patients at terminal stage.

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Breast cancer with metastasis especially brain metastasis represents a significant cause of morbidity and mortality in patients. In this study, we aimed to investigate the hub genes and potential molecular mechanism in brain metastasis breast cancer. Expression profiles of the genes were extracted from the Gene Expression Omnibus (GEO) database. GO and KEGG pathway enrichment analyses were conducted at Database for Annotation, Visualization, and Integrated Discovery. Protein-protein interaction (PPI) network was established by STRING database constructed by Cytoscape software. Hub genes were identified by the molecular complex detection (MCODE) plugin and the CytoHubba plugin. The transcription factor (TF) that regulates the expression of hub genes was analyzed using the NetworkAnalyst algorithm. Kaplan-Meier curve was used to analyze the effects of hub genes on overall survival. Two GEO databases (GSE100534 and GSE52604) were downloaded from GEO databases. A total of 102 overlapped genes were identified, and the top five KEGG pathways enriched were pathways in cancer, HTLV-I infection, focal adhesion, ECM-receptor interaction, and protein digestion and absorption. By combing the results of MCODE and CytoHubba, a total of 10 hub genes were selected. Kaplan-Meier curve showed that ANLN, BUB1, TTK, and SKA3 were closely associated with the overall survival of breast cancer patients. TF analysis results showed that E2F4, KDM5B, and MYC were crucial regulators for these four hub genes. The current study based on the GEO database provided novel understanding regarding the mechanism of breast cancer metastasis to brain and may provide novel therapeutic targets.bioinformatics, breast cancer brain metastasis (BCBM), differentially expressed genes (DEGs), functional enrichment analysis, prognosis, regulatory network 1 | INTRODUCTION Breast cancer (BC) was estimated to have 2.1 million newly diagnosed cases in 2018 in the worldwide range. 1 It was estimated that 20% to 30% BC patients will experience distant metastasis. 2 The worst is that the median overall survival (OS) for metastasis BC is only 2 to 3 years, while the 5-year OS is merely 25%. 3 Brain metastasis (BM) is the most commonly diagnosed intracranial tumor as its incidence is significantly higher than the primary brain cancer. 4 The top three sources for BM in descending order are lung cancer, BC, and melanoma. 5 J Cell Biochem. 2019;120:9522-9531. wileyonlinelibrary.com/journal/jcb 9522 |

Paclitaxel prodrug based mixed micelles with high drug loading and tumor targeting capacity for elevated chemotherapy.