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Anti-angiogenics in Brain Metastases: Perspectives and Experiences

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Tumor Angiogenesis

Abstract

Metastasis to the brain is an increasing complication of solid cancers, associated with high morbidity and mortality. Our understanding of key molecular and cellular determinants of early brain colonization and metastatic growth has significantly increased in the last decade, including crucial interactions with brain blood vessels. In lung adenocarcinoma, an early angiogenic switch appears mandatory for outgrowth beyond a micrometastatic state. This can explain preventive effects of anti-angiogenics against brain metastases formation in lung adenocarcinoma, which are suggested by mouse experiments and retrospective analysis of a clinical trial. Interestingly, there is no indication that those preventive effects of anti-angiogenics against the formation of macrometastases can be found outside the brain or in other tumor entities. In established brain macrometastases of various cancers, a growth pattern with strong angiogenic features can frequently be observed. Accordingly, an increasing amount of data speaks for a clinically meaningful activity of anti-angiogenics, particularly the anti-VEGF-A antibody bevacizumab, against brain macrometastases of patients. Moreover, the antiedema effects of this class of drugs, including their activity against radionecrosis, make anti-angiogenics useful agents in clinical practice with beneficial effects on neurological deficits and quality of life. This is even true for anti-angiogenics like bevacizumab given as single agents without combined chemotherapy. Taken together, there is accumulating evidence that anti-angiogenics might have a particularly meaningful role in the prevention and treatment of brain metastases. The lack of prospective randomized trials means that they have to be considered experimental therapies in this situation today. Thus, more robust clinical data are necessary to fully clarify the role of anti-angiogenics in brain metastases, a disease where better strategies for prevention and treatment are urgently needed.

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Acknowledgments

This work was funded by the Deutsche Krebshilfe (German Cancer Aid), Priority Program “Translational Oncology”, #70112507, “Preventive strategies against brain metastases.”

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Authors and Affiliations

  1. Neurology Clinic, University Hospital Heidelberg, Heidelberg, Germany

    Frank Winkler

  2. German Cancer Research Center, Heidelberg, Germany

    Frank Winkler

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  1. Frank Winkler
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Correspondence to Frank Winkler .

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Editors and Affiliations

  1. Tumor Biology Center, Freiburg, Baden-Württemberg, Germany

    Dieter Marmé

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Winkler, F. (2019). Anti-angiogenics in Brain Metastases: Perspectives and Experiences. In: Marmé, D. (eds) Tumor Angiogenesis. Springer, Cham. https://doi.org/10.1007/978-3-319-33673-2_49

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