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Overexpression of human epidermal growth factor receptor 2 (HER2) in breast cancer patients is associated with increased incidence of breast cancer brain metastases (BCBM), but the mechanisms underlying this phenomenon remain unclear. Here, to identify brain-predominant genes critical for the establishment of BCBM, we conducted an in silico screening analysis and identified that increased levels of fatty acid binding protein 7 (FABP7) correlate with lower survival and higher incidence of brain metastases in breast cancer patients. We validated these findings using HER2+ BCBM cells compared to parental breast cancer cells. Importantly, through knockdown and overexpression assays we characterized the role of FABP7 in the BCBM process in vitro and in vivo. Our results uncover a key role of FABP7 in metabolic reprogramming of HER2+ breast cancer cells, supporting a glycolytic phenotype and storage of lipid droplets that enable their adaptation and survival in the brain microenvironment. Additionally, FABP7 is shown to be required for up-regulation of key metastatic genes and pathways, such as Integrins-Src and VEGFA, and for the growth of HER2+ breast cancer cells in the brain microenvironment in vivo. Together our results support FABP7 as a potential target for the treatment of HER2+ BCBM.

Introduction Glioblastoma (GBM) is the most aggressive malignant brain cancer in adults, and its poor prognosis and resistance to the existing standard of care require the development of innovative therapeutic modalities. The local delivery of stem cells as therapeutic carriers against glioma has produced encouraging results, but encounters obstacles with regards to the repeatability and invasiveness of administration. Intranasal delivery of therapeutic stem cells could overcome these obstacles, among others, as a noninvasive and easily repeatable mode of administration. Areas covered This review describes nasal anatomy, routes of stem cell migration, and factors affecting stem cell delivery to hard-to-reach tumors. Furthermore, this review discusses the molecular mechanisms underlying stem cell migration following delivery, as well as possible stem cell effector functions to be considered in combination with intranasal delivery. Expert opinion Further research is necessary to elucidate the dynamics of stem cell effector functions in the context of intranasal delivery and optimize their therapeutic potency. Nonetheless, the technique represents a promising tool against brain cancer and has the potential to be expanded for use against other brain pathologies.