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An Insight into Molecular Targets of Breast Cancer Brain Metastasis.

ABSTRACT: Brain metastasis is one of the major reasons of death in breast cancer (BC) patients, significantly affecting the quality of life, physical activity, and interdependence on several individuals. There is no clear evidence in scientific literature that depicts an exact mechanism relating to brain metastasis in BC patients. The tendency to develop breast cancer brain metastases (BCBMs) differs by the BC subtype, varying from almost half with triple-negative breast cancer (TNBC) (HER2^- ER^- PR^-), one-third with HER2⁺ (human epidermal growth factor receptor 2-positive, and around one-tenth with luminal subclass (ER⁺ (estrogen positive) or PR⁺ (progesterone positive)) breast cancer. This review focuses on the molecular pathways as possible therapeutic targets of BCBMs and their potent drugs under different stages of clinical trial. In view of increased numbers of clinical trials and systemic studies, the scientific community is hopeful of unraveling the underlying mechanisms of BCBMs that will help in designing an effective treatment regimen with multiple molecular targets.

SUBMITTER: Kaleem M

PROVIDER: S-EPMC9569595 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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An Insight into Molecular Targets of Breast Cancer Brain Metastasis.

Kaleem Mohammed M Dalhat Mahmood Hassan MH Azmi Lubna L Asar Turky Omar TO Ahmad Wasim W Alghanmi Maimonah M Almostadi Amal A Zughaibi Torki A TA Tabrez Shams S

International journal of molecular sciences 20221002 19

Brain metastasis is one of the major reasons of death in breast cancer (BC) patients, significantly affecting the quality of life, physical activity, and interdependence on several individuals. There is no clear evidence in scientific literature that depicts an exact mechanism relating to brain metastasis in BC patients. The tendency to develop breast cancer brain metastases (BCBMs) differs by the BC subtype, varying from almost half with triple-negative breast cancer (TNBC) (HER2<sup>-</sup> ER ...[more]

PMID: 36232989

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Project description:IntroductionThe incidence of brain metastases in cancer patients is increasing, with lung and breast cancer being the most common sources. Despite advancements in targeted therapies, the prognosis remains poor, highlighting the importance to investigate the underlying mechanisms in brain metastases. The aim of this study was to investigate the differences in the molecular mechanisms involved in brain metastasis of breast and lung cancers. In addition, we aimed to identify cancer lineage-specific druggable targets in the brain metastasis.MethodsTo that aim, a cohort of 44 FFPE tissue samples, including 22 breast cancer and 22 lung adenocarcinoma (LUAD) and their matched-paired brain metastases were collected. Targeted gene expression profiles of primary tumors were compared to their matched-paired brain metastases samples using nCounter PanCancer IO 360™ Panel of NanoString technologies. Pathway analysis was performed using gene set analysis (GSA) and gene set enrichment analysis (GSEA). The validation was performed by using Immunohistochemistry (IHC) to confirm the expression of immune checkpoint inhibitors.ResultsOur results revealed the significant upregulation of cancer-related genes in primary tumors compared to their matched-paired brain metastases (adj. p ≤ 0.05). We found that upregulated differentially expressed genes in breast cancer brain metastasis (BM-BC) and brain metastasis from lung adenocarcinoma (BM-LUAD) were associated with the metabolic stress pathway, particularly related to the glycolysis. Additionally, we found that the upregulated genes in BM-BC and BM-LUAD played roles in immune response regulation, tumor growth, and proliferation. Importantly, we identified high expression of the immune checkpoint VTCN1 in BM-BC, and VISTA, IDO1, NT5E, and HDAC3 in BM-LUAD. Validation using immunohistochemistry further supported these findings.ConclusionIn conclusion, the findings highlight the significance of using matched-paired samples to identify cancer lineage-specific therapies that may improve brain metastasis patients outcomes.

Dataset Information

An Insight into Molecular Targets of Breast Cancer Brain Metastasis.

Publications

An Insight into Molecular Targets of Breast Cancer Brain Metastasis.

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