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Updated: Mar 18, 2026
Modeling Brain Metastasis by Internal Carotid Artery Injection of Cancer Cells
Published on: August 2, 2022
Dissection of the Process of Brain Metastasis Reveals Targets and Mechanisms for Molecular-based Intervention
Ulrich H Weidle1, Fabian Birzele2, Gwendlyn Kollmorgen1
1Roche Innovation Center Munich, Roche Diagnostics GmbH, Penzberg, Germany.
Abstract:
Brain metastases outnumber the incidence of brain tumors by a factor of ten. Patients with brain metastases have a dismal prognosis and current treatment modalities achieve only a modest clinical benefit. We discuss the process of brain metastasis with respect to mechanisms and involved targets to outline options for therapeutic intervention and focus on breast and lung cancer, as well as melanoma. We describe the process of penetration of the blood-brain-barrier (BBB) by disseminated tumor cells, establishment of a metastatic niche, colonization and outgrowth in the brain parenchyma. Furthermore, the role of angiogenesis in colonization of the brain parenchyma, interactions of extravasated tumor cells with microglia and astrocytes, as well as their propensity for neuromimicry, is discussed. We outline targets suitable for prevention of metastasis and summarize targets suitable for treatment of established brain metastases. Finally, we highlight the implications of findings revealing druggable mutations in brain metastases that cannot be identified in matching primary tumors.
Insights
Brain metastases, common in cancer patients, have poor prognoses. This review details brain metastasis mechanisms, therapeutic targets, and highlights druggable mutations in metastases.
Area of Science:
- Oncology
- Neuroscience
- Cancer Biology
Background:
- Brain metastases are more common than primary brain tumors, with limited treatment options and poor patient prognosis.
- Understanding the mechanisms of brain metastasis is crucial for developing effective therapies.
Purpose of the Study:
- To review the process of brain metastasis, focusing on breast cancer, lung cancer, and melanoma.
- To identify therapeutic targets for preventing and treating brain metastases.
- To discuss the implications of genetic mutations found in brain metastases.
Main Methods:
- Review of existing literature on brain metastasis mechanisms.
- Analysis of tumor cell interactions with the brain microenvironment.
- Identification of molecular targets for therapeutic intervention.
Main Results:
- Disseminated tumor cells penetrate the blood-brain barrier (BBB), establish niches, and colonize the brain.
- Angiogenesis, microglia/astrocyte interactions, and cancer cell neuromimicry play key roles in brain colonization.
- Druggable mutations are present in brain metastases, sometimes distinct from primary tumors.
Conclusions:
- Targeting specific mechanisms of brain metastasis, such as BBB penetration and niche formation, offers therapeutic potential.
- Exploiting unique mutations in brain metastases may lead to personalized treatment strategies.
- Further research into the biology of brain metastases is essential for improving patient outcomes.
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