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- W2741751854 abstract "Patients with breast cancer brain metastases (BCBM) suffer from a devastating outcome despite recent progress in a variety of therapeutic modality. Among the four major molecular subtypes, breast cancers that are either human epidermal growth factor receptor (HER) 2- positive or triple-negative breast cancer (TNBC) patients have a higher risk of BCBM compared with the luminal cancer patients. The mechanisms by which the disseminated cancer cells overcome the multistep defense mechanism in the brain, adapt the microenvironment, and subsequently initiate metastasis remain elusive. Recently, we identified a set of genes that contribute to initiate Glioblastoma (GBM) and at least some of them are functionally essential for GBM establishment and the therapy resistance. Mixed lineage kinase 4 (MLK4) is a relatively poorly characterized serine/threonine kinase, which is largely expressed in various cancers including GBM. We recently found a critical role of MLK4 in controlling the mesenchymal identity in GBM stem cells and plays a role in GBM initiation through direct activation of NF-kB signaling. Our preliminary data indicates MLK4 is also highly expressed in patient-derived hormone receptor (HR)-negative breast cancer cells in comparison with the other HR-positive counterparts. For therapeutic development purpose, we performed the structure-based drug design, which has led to identify two small molecule MLK4 inhibitor candidates to test efficacy on a set of patient-derived breast cancer cells in vitro and their xenografted tumors in vivo. Results will be presented in the conference. Citation Format: Heba Allah M. Alsheikh, Mutsuko Minata, Shinobu Yamaguchi, Ichiro Nakano. Mesenchymal identity of breast cancer promotes brain metastases and therapeutic resistance through MLK4/NFkB signaling Pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 869. doi:10.1158/1538-7445.AM2017-869" @default.
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- W2741751854 date "2017-07-01" @default.
- W2741751854 modified "2023-09-27" @default.
- W2741751854 title "Abstract 869: Mesenchymal identity of breast cancer promotes brain metastases and therapeutic resistance through MLK4/NFkB signaling Pathway" @default.
- W2741751854 doi "https://doi.org/10.1158/1538-7445.am2017-869" @default.
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