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Intracarotid Cancer Cell Injection to Produce Mouse Models of Brain Metastasis
Published on: February 8, 2017
Recent advances in breast cancer metastasis with special emphasis on metastasis to the brain
Fairooz Labiba Sadique1, Hemavathy Subramaiam2, Purushotham Krishnappa2
1Department of Biomedical Science, School of Health Sciences, International Medical University, Kuala Lumpur 57000, Malaysia.
Abstract:
Understanding the underlying mechanisms of breast cancer metastasis is of vital importance for developing treatment approaches. This review emphasizes contemporary breakthrough studies with special focus on breast cancer brain metastasis. Acquired mutational changes in metastatic lesions are often distinct from the primary tumor, suggesting altered mutagenesis pathways. The concept of micrometastases and heterogeneity within the tumors unravels novel therapeutic targets at genomic and molecular levels through epigenetic and proteomic profiling. Several pre-clinical studies have identified mechanisms involving the immune system, where tumor associated macrophages are key players. Expression of cell proteins like Syndecan1, fatty acid-binding protein 7 and tropomyosin kinase receptor B have been implicated in aiding the transmigration of breast cancer cells to the brain. Changes in the proteomic landscape of the blood-brain-barrier show altered permeability characteristics, supporting entry of cancer cells. Findings from laboratory studies pave the path for the emergence of new biomarkers, especially blood-based miRNA and circulating tumor cell markers for prognostic staging. The constantly evolving therapeutics call for clinical trials backing supportive evidence of efficacies of both novel and existing approaches. The challenge lying ahead is discovering innovative techniques to replace use of human samples and optimize small-scale patient recruitment in trials.
Insights
Understanding breast cancer brain metastasis is key for new treatments. Research highlights genetic changes, immune roles, and protein markers aiding cancer spread, leading to new biomarkers and clinical trial needs.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Breast cancer metastasis is a critical challenge in treatment development.
- Metastatic lesions often exhibit distinct genetic alterations from primary tumors.
- Understanding mechanisms of metastasis, particularly to the brain, is vital.
Purpose of the Study:
- To review contemporary studies on breast cancer metastasis, focusing on brain metastasis.
- To highlight novel therapeutic targets identified through genomic, molecular, and proteomic profiling.
- To discuss emerging biomarkers and the need for clinical validation.
Main Methods:
- Review of contemporary breakthrough studies.
- Analysis of genomic and molecular profiling data.
- Examination of pre-clinical studies on immune system involvement and protein expression.
Main Results:
- Acquired mutations in metastatic sites suggest altered mutagenesis pathways.
- Tumor-associated macrophages play a key role in metastasis.
- Specific proteins (Syndecan1, FABP7, TrkB) and blood-brain barrier changes facilitate brain metastasis.
- Emerging biomarkers include blood-based microRNAs and circulating tumor cells.
Conclusions:
- Genomic and proteomic insights reveal novel therapeutic targets.
- Immune system modulation and targeting specific proteins are promising strategies.
- Development of blood-based biomarkers is crucial for prognostic staging.
- Clinical trials are essential to validate novel and existing therapeutic approaches.
