An estimated 20% of all patients with cancer will develop brain metastases, with the majority of brain metastases occurring in those with lung, breast and colorectal cancers, melanoma or renal cell carcinoma. Brain metastases are thought to occur via seeding of circulating tumour cells into the brain microvasculature; within this unique microenvironment, tumour growth is promoted and the penetration of systemic medical therapies is limited. Development of brain metastases remains a substantial contributor to overall cancer mortality in patients with advanced-stage cancer because prognosis remains poor despite multimodal treatments and advances in systemic therapies, which include a combination of surgery, radiotherapy, chemotherapy, immunotherapy and targeted therapies. Thus, interest abounds in understanding the mechanisms that drive brain metastases so that they can be targeted with preventive therapeutic strategies and in understanding the molecular characteristics of brain metastases relative to the primary tumour so that they can inform targeted therapy selection. Increased molecular understanding of the disease will also drive continued development of novel immunotherapies and targeted therapies that have higher bioavailability beyond the blood–tumour barrier and drive advances in radiotherapies and minimally invasive surgical techniques. As these discoveries and innovations move from the realm of basic science to preclinical and clinical applications, future outcomes for patients with brain metastases are almost certain to improve.
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Nature Reviews Disease Primers thanks M. Davies, G. Rao, J. Saunus, and other anonymous reviewer(s), for their contribution to the peer review of this work.
C.A. has received funding support from Novartis, Merrimack, PUMA, Lilly, Merck, Cascadian/Seattle Genetics, Nektar, Tesaro and G1-Therapuetics; she has held uncompensated advisory roles with Novartis, Merrimack, Lilly, Genentech, Nektar and Cascadian/Seattle Genetics; she has held compensated advisory roles with PUMA, Merck and Eisai; and she has received royalties from UpToDate, Jones and Bartlett. M.S.A. has stock options in MimiVax and Doctible and has received grants and/or personal fees from Monteris Medical, AbbVie, BMS, AstraZeneca, Datar Genetics, CBT Pharmaceuticals, Kadmon Pharmaceuticals, Elsevier, NovoCure, Novartis, Incyte, Pharmacyclics, Tracon Pharmaceuticals, Prime Oncology, Flatiron, Merck, Bayer, Varian Medical Systems, VBI Vaccines and Caris Lifesciences. S.P. receives honoraria or consultation fees from AbbVie, Amgen, AstraZeneca, Bayer, Biocartis, Boehringer-Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffmann-La Roche, Foundation Medicine, Illumina, Janssen, Merck Sharp and Dohme, Merck Serono, Merrimack, Novartis, Pharma Mar, Pfizer, Regeneron, Sanofi, Seattle Genetics and Takeda; she has given talks in an organized public event for AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp and Dohme, Novartis, Pfizer and Takeda; and she is a (sub)investigator in trials (institutional financial support for clinical trials) sponsored by Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Clovis, F. Hoffmann-La Roche, Illumina, Merck Sharp and Dohme, Merck Serono, Novartis, MedImmune and Pfizer. P.S.S. receives research funding from MedImmune. The remaining authors declare no competing interests.
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Achrol, A.S., Rennert, R.C., Anders, C. et al. Brain metastases. Nat Rev Dis Primers 5, 5 (2019). https://doi.org/10.1038/s41572-018-0055-y
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