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Breast cancer brain metastasis: molecular mechanisms and directions for treatment.

ABSTRACT: The development of brain metastasis (BM) of breast cancer is usually a late event with deleterious effect on the prognosis. Treatment options for intracerebral seeding of breast cancer are limited and, so far, nonspecific. Molecular detailing of subsequent events of penetration, seeding, and outgrowth in brain is highly relevant for developing therapeutic strategies to treat, or prevent, BM.We scrutinize recent literature for molecules and pathways that are operative in the formation of breast cancer BM. We also summarize current data on therapeutic efforts to specifically address BM of breast cancer. Data on molecular pathways underlying the formation of BM of breast cancer are sketchy and to some extent inconsistent. The molecular makeup of BM differs from that of the primary tumors, as well as from metastases at other sites. Current efforts to treat breast cancer BM are limited, and drugs used have proven effects on the primary tumors but lack specificity for the intracerebral tumors.More basic research is necessary to better characterize BM of breast cancer. Apart from the identification of drug targets defined by the intracerebral tumors, also targets in the molecular pathways involved in passing the blood-brain barrier and intracerebral tumor cell growth should be revealed.

SUBMITTER: Pedrosa RMSM

PROVIDER: S-EPMC6176797 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Breast cancer brain metastasis: molecular mechanisms and directions for treatment.

Pedrosa Rute M S M RMSM Mustafa Dana A DA Soffietti Riccardo R Kros Johan M JM

Neuro-oncology 20181001 11

The development of brain metastasis (BM) of breast cancer is usually a late event with deleterious effect on the prognosis. Treatment options for intracerebral seeding of breast cancer are limited and, so far, nonspecific. Molecular detailing of subsequent events of penetration, seeding, and outgrowth in brain is highly relevant for developing therapeutic strategies to treat, or prevent, BM.We scrutinize recent literature for molecules and pathways that are operative in the formation of breast c ...[more]

PMID: 29566179

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Project description:Metastasis is the main cause of breast cancer‑related mortalities. The present study aimed to uncover the relevant molecular mechanisms of breast cancer metastasis and to explore potential biomarkers that may be used for prognosis. Expression profile microarray data GSE8977, which contained 22 stroma samples (15 were from normal breast and 7 were from invasive ductal carcinoma tumor samples), were obtained from the Gene Expression Omnibus database. Following data preprocessing, differentially expressed genes (DEGs) were selected based on analyses conducted using the linear models for microarray analysis package from R and Bioconductor software. The resulting data were used in subsequent function and pathway enrichment analyses, as well as protein‑protein interaction (PPI) network and subnetwork analyses. Transcription factors (TFs) and tumor‑associated genes were also identified among the DEGs. A total of 234 DEGs were identified, which were enriched in immune response, cell differentiation and cell adhesion‑related functions and pathways. Downregulated DEGs included TFs, such as the proto‑oncogene SPI1, pre‑B‑cell leukemia homeobox 3 (PBX3) and lymphoid enhancer‑binding factor 1 (LEF1), as well as tumor suppressors (TSs), such as capping actin protein, gelsolin like (CAPG) and tumor protein p53‑inducible nuclear protein 1 (TP53INP1). Upregulated DEGs also included TFs and tumor suppressors, consisting of transcription factor 7‑like 2 (TCF7L2) and pleiomorphic adenoma gene‑like 1 (PLAGL1). DEGs that were identified at the hub nodes in the PPI network and the subnetwork were epidermal growth factor receptor (EGFR) and spleen‑associated tyrosine kinase (SYK), respectively. Several genes crucial in the metastasis of breast cancer were identified, which may serve as potential biomarkers, many of which were associated with cell adhesion, proliferation or immune response, and may influence breast cancer metastasis by regulating these function or pathways.

Dataset Information

Breast cancer brain metastasis: molecular mechanisms and directions for treatment.

Publications

Breast cancer brain metastasis: molecular mechanisms and directions for treatment.

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