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Brain metastasis

Nature Reviews Cancer volume 20, pages 4–11 (2020)Cite this article

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Abstract

Brain metastasis, which commonly arises in patients with lung cancer, breast cancer and melanoma, is associated with poor survival outcomes and poses distinct clinical challenges. The brain microenvironment, with its unique cell types, anatomical structures, metabolic constraints and immune environment, differs drastically from microenvironments of extracranial lesions, imposing a distinct and profound selective pressure on tumour cells that, in turn, shapes the metastatic process and therapeutic responses. Accordingly, the study of brain metastasis could uncover new therapeutic targets and identify novel treatment approaches to address the unmet clinical need. Moreover, such efforts could provide insight into the biology of primary brain tumours, which face similar challenges to brain metastases of extracranial origin, and vice versa. However, the paucity of robust preclinical models of brain metastasis has severely limited such investigations, underscoring the importance of developing improved experimental models that holistically encompass the metastatic cascade and/or brain microenvironment. In this Viewpoint, we asked four leading experts to provide their opinions on these important aspects of brain metastasis biology and management.

The contributors

Adrienne Boire is an assistant attending neurologist and assistant member of the Human Oncology and Pathogenesis Program at Memorial Sloan Kettering Cancer Center, New York, USA. Her clinical and basic science research focuses on leptomeningeal metastases. Her laboratory research programme focuses on microenvironmental interactions between cancer cells and the leptomeninges, and her clinical practice and research focuses on the care of patients with leptomeningeal metastasis.

Priscilla Brastianos is the Director of the Central Nervous System Metastasis Center at Massachusetts General Hospital and Harvard Medical School, Boston, USA. Her research focuses on understanding the molecular mechanisms that drive brain metastasis. Her work demonstrates that brain metastases show branched or divergent evolution, and harbour clinically significant drivers that are distinct from clinically sampled primary tumours. She has translated her scientific findings to national multicentre trials. She also leads a multidisciplinary central nervous system metastasis clinic at Massachusetts General Hospital and Harvard Medical School.

Livia Garzia is an assistant professor with the Department of Surgery, Division of Orthopaedic Surgery at McGill University and a principal investigator at the Research Institute of the McGill University Health Centre, in Montreal, Canada. The main focus of her laboratory is to understand the mechanisms of metastasis and relapse in paediatric solid tumours such as sarcomas and brain tumours. Her research has uncovered the role of haematogenous dissemination of medulloblastoma tumour cells to leptomeningeal metastasis.

Manuel Valiente is the Head of the Brain Metastasis Group at the National Cancer Research Center (CNIO) in Madrid, Spain. His main interest is to study the mechanisms used by metastatic cells to adapt to the brain and to understand how this process modifies both cancer cells and brain cells. His research has proved that the underlying molecular regulation of organ adaptation can be exploited therapeutically using novel strategies.

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Acknowledgements

M.V. acknowledges support from the Ministry of Economy and Competitiveness (MINECO) grant MINECO-Retos SAF2017-89643-R, the Bristol-Myers Squibb–Melanoma Research Alliance Young Investigator Award 2017 (498103), the Beug Foundation’s Prize for Metastasis Research 2017, Fundación Ramón Areces (CIVP19S8163), Worldwide Cancer Research (19-0177), Horizon 2020 Funding and Emerging Technologies (FET) Open (828972), the Clinic and Laboratory Integration Program Cancer Research Institute (CRI) Award 2018 (54545) and Spanish Association Against Cancer (AECC) Coordinated Translational Groups 2017 (GCTRA16015SEOA). M.V. is a Ramón y Cajal Investigator (RYC-2013-13365) and a member of the European Molecular Biology Organization Young Investigator Programme (EMBO YIP; 4053). L.G. is supported by CIHR Operating Grant PJT-162234, Terry Fox Research Institute grant TFRI1087, Canadian Cancer Society Research Institute CCS#705799, the Cancer Research Society and the C17 Research Network.

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Authors and Affiliations

  1. Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Adrienne Boire

  2. Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA

    Priscilla K. Brastianos

  3. Research Institute of the McGill University Health Centre, Montreal, Québec, Canada

    Livia Garzia

  4. National Cancer Research Center, Madrid, Spain

    Manuel Valiente

Authors
  1. Adrienne Boire
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  2. Priscilla K. Brastianos
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  3. Livia Garzia
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  4. Manuel Valiente
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Corresponding authors

Correspondence to Adrienne Boire, Priscilla K. Brastianos, Livia Garzia or Manuel Valiente.

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Competing interests

A.B. is a Consultant for Arix Biosciences, and has patents related to methods for treating brain metastasis (US Patent 10,413,522) and modulating permeability of the blood–CSF barrier (US Provisional Application Number 62/258,044). P.B. has consulted for Lilly, Genentech–Roche, AngioChem and Tesaro, has received speakers honoraria from Merck and Genentech–Roche, and has received research funding from Merck, Bristol-Myers Squibb and Pfizer. The other authors declare no competing interests.

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Boire, A., Brastianos, P.K., Garzia, L. et al. Brain metastasis. Nat Rev Cancer 20, 4–11 (2020). https://doi.org/10.1038/s41568-019-0220-y

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