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Leveraging translational insights toward precision medicine approaches for brain metastases

Nature Cancer volume 4, pages 955–967 (2023)Cite this article

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Abstract

Due to increasing incidence and limited treatments, brain metastases (BM) are an emerging unmet need in modern oncology. Development of effective therapeutics has been hindered by unique challenges. Individual steps of the brain metastatic cascade are driven by distinctive biological processes, suggesting that BM possess intrinsic biological differences compared to primary tumors. Here, we discuss the unique physiology and metabolic constraints specific to BM as well as emerging treatment strategies that leverage potential vulnerabilities.

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Fig. 1: The brain metastatic cascade.
Fig. 2: Simplified schematic of BBB and BTB physiology and potential therapeutic strategies.
Fig. 3: A translational workflow in analyzing patient-derived BM tissue and identifying new therapeutic targets.

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Acknowledgements

We acknowledge helpful feedback from G.P. Perrino. P.K.B. is supported by the NCI (1R01CA227156-01 and 1R01CA244975-01), Terry and Jean de Gunzburg MGH Research Scholar Fund, Victoria’s Secret Global Fund for Women’s Cancers Rising Innovator Research Grant, in Partnership with Pelotonia and AACR, and the Breast Cancer Research Foundation. A.E.K. is supported by an American Brain Tumor Association Basic Research Fellowship in honor of Paul Fabbri (BRF1900017), the William G. Kaelin, Jr., MD, Physician–Scientist Award of the Damon Runyon Cancer Research Foundation, an American Association for Cancer Research Breast Cancer Research Fellowship and an American Society of Clinical Oncology/Conquer Cancer Young Investigator Award.

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  1. These authors contributed equally: Edwin Nieblas-Bedolla, Magali A. de Sauvage.

Authors and Affiliations

  1. Center for Cancer Research, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA

    Albert E. Kim, Edwin Nieblas-Bedolla, Magali A. de Sauvage & Priscilla K. Brastianos

  2. Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Albert E. Kim

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Correspondence to Priscilla K. Brastianos.

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P.K.B. has consulted for Tesaro, Angiochem, Genentech–Roche, ElevateBio, Axiom Healthcare Strategies, Eli Lilly, SK Life Science, Pfizer, Voyager Therapeutics, Sintetica, MPM Capital Advisers, Advise Connect Inspire, Kazia, CraniUS and Dantari; has received institutional research funding (to Massachusetts General Hospital) from Merck, Mirati, Eli Lilly, BMS, Kinnate and Pfizer; has received clinical trial support (to institution) from AstraZeneca, Eli Lilly, Pfizer, Bristol Myers Squibb, Genentech–Roche, GSK and Merck; and has received honoraria from Merck, Medscape, Pfizer and Genentech–Roche. The remaining authors declare no competing interests.

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Kim, A.E., Nieblas-Bedolla, E., de Sauvage, M.A. et al. Leveraging translational insights toward precision medicine approaches for brain metastases. Nat Cancer 4, 955–967 (2023). https://doi.org/10.1038/s43018-023-00585-0

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