Brain metastasis

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. In this Viewpoint article, we asked four experts to provide their opinions on important aspects of brain metastasis biology, focusing on the unique microenvironment and therapeutic targets in the brain, preclinical models and how studying brain metastases could inform primary brain tumour biology. 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.