4.7 Article

Preclinical Models of Brain Metastases in Breast Cancer

Journal

BIOMEDICINES
Volume 10, Issue 3, Pages -

Publisher

MDPI
DOI: 10.3390/biomedicines10030667

Keywords

breast cancer; brain metastasis; preclinical animal models; patient-derived xenografts; animal imaging; multimodal imaging

Funding

  1. Young Investigator Startup Grant, Department of Surgery, Western University, London, ON
  2. Clinician Scientist Award, Department of Surgery, Western University
  3. Academic Medical Organization of Southwestern Ontario (AMOSO) Opportunities Fund (London, ON)
  4. Ontario Graduate Scholarship (OGS)
  5. Translational Breast Cancer Research Unit Trainee Scholarship (Breast Cancer Society of Canada), London, ON
  6. Translational Breast Cancer Research Unit Trainee Scholarship (Breast Cancer Society of Canada)
  7. Canadian Institutes for Health Research
  8. Natural Sciences and Engineering Research Council of Canada
  9. National Institute of Neurological Disorders and Stroke
  10. National Cancer Institute

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Breast cancer brain metastases (BCBM) are a major cause of female mortality worldwide. The scarcity of representative experimental preclinical models has hindered the advancement of BCBM treatment. However, recent developments in patient-derived in vitro and in vivo breast cancer culturing systems, along with advances in animal brain imaging, have provided opportunities to better understand BCBM biology and develop novel treatment approaches.
Breast cancer remains a leading cause of mortality among women worldwide. Brain metastases confer extremely poor prognosis due to a lack of understanding of their specific biology, unique physiologic and anatomic features of the brain, and limited treatment strategies. A major roadblock in advancing the treatment of breast cancer brain metastases (BCBM) is the scarcity of representative experimental preclinical models. Current models are predominantly based on the use of animal xenograft models with immortalized breast cancer cell lines that poorly capture the disease's heterogeneity. Recent years have witnessed the development of patient-derived in vitro and in vivo breast cancer culturing systems that more closely recapitulate the biology from individual patients. These advances led to the development of modern patient-tissue-based experimental models for BCBM. The success of preclinical models is also based on the imaging technologies used to detect metastases. Advances in animal brain imaging, including cellular MRI and multimodality imaging, allow sensitive and specific detection of brain metastases and monitoring treatment responses. These imaging technologies, together with novel translational breast cancer models based on patient-derived cancer tissues, represent a unique opportunity to advance our understanding of brain metastases biology and develop novel treatment approaches. This review discusses the state-of-the-art knowledge in preclinical models of this disease.

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