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Targeted Therapies for the Treatment of Brain Metastases in Solid Tumors

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Abstract

Brain metastases are a major cause of morbidity and mortality in cancer patients. While the mainstay treatment comprises surgery and radiation therapy, the role of systemic agents remains controversial. In general, it has been presumed that poor blood–brain barrier (BBB) penetration and inherently more resistant metastatic brain disease preclude a favorable systemic treatment approach. However, a better understanding of tumor biology and the subsequent development of targeted drugs have reawakened interest in systemic therapy. Despite still limited brain distribution, a variety of targeted drugs have demonstrated activity in brain metastases in early clinical trials. Nevertheless, disease progression commonly occurs, and it remains to be elucidated whether limited CNS drug distribution or the acquisition of resistant metastatic clones must be held responsible for this prognosis. Moreover, micrometastatic brain disease beyond an intact BBB—and ultimately prevention of brain metastasis formation—may generally remain inaccessible for first-generation targeted agents with poor CNS penetration. To overcome limited brain distribution and possibly emerging acquired resistance, highly potent next-generation targeted drugs with enhanced CNS distribution have been developed. In view of this emerging but yet undefined role of targeted therapies in the treatment of brain metastases from solid tumors, this review aims to summarize the current knowledge from clinical trials and discusses clinically relevant obstacles to overcome.

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Authors and Affiliations

  1. Department of Internal Medicine V, Medical University of Innsbruck, Anichstrasse 35, A-6020, Innsbruck, Austria

    Jan-Paul Bohn, Georg Pall & Michael Steurer

  2. Department of Neurology and Neurosurgery, Medical University of Innsbruck, Innsbruck, Austria

    Guenther Stockhammer

Authors
  1. Jan-Paul Bohn
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  2. Georg Pall
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  3. Guenther Stockhammer
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  4. Michael Steurer
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Correspondence to Jan-Paul Bohn.

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Funding

Jan-Paul Bohn reports an unrestricted scientific grant from Mundipharma.

Conflicts of interest

Georg Pall reports personal fees from Roche, Boehringer Ingelheim, Novartis and Pfizer for advisory board participation and lectures. Jan-Paul Bohn, Guenther Stockhammer and Michael Steurer declare that they have no conflict of interest.

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Bohn, JP., Pall, G., Stockhammer, G. et al. Targeted Therapies for the Treatment of Brain Metastases in Solid Tumors. Targ Oncol 11, 263–275 (2016). https://doi.org/10.1007/s11523-015-0414-5

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  • DOI: https://doi.org/10.1007/s11523-015-0414-5

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