Abstract: Brain metastases are clinically devastating. Up to 25% of cancer patients will develop brain metastases and prognosis in this patient population continues to be poor. The vast majority of clinical trials in the US exclude patients with active brain metastases. Our understanding of how intracranial metastases genetically evolve from primary tumors has historically been limited, which has hampered the development of clinical trials for this patient population. In this presentation, I will present our ongoing work on genomic characterization of central nervous system metastases with a comparison to primary tumors and extracranial sites. Intracranial metastases demonstrate branched evolution, whereby the brain metastases and primary tumors share a common genetic ancestor yet both the primary tumor and brain metastasis continue to evolve independently.  We also show that comprehensive genomic characterization of brain metastases, coupled with functional validation in mouse models of metastasis, can lead to the discovery of putative drivers of progression and metastasis. Taken together, our data implies that precision medicine approaches based solely on genetic characterization of extracranial sites tumors may miss potential therapeutic targets from which patients with brain metastases might benefit.    Importantly, despite genetic heterogeneity between the brain metastases and extracranial sites, there are common clinically actionable genetic alterations across brain metastases of different histologies. We have translated these findings to clinical trials, including an NCI-sponsored cooperative group genomically-guided clinical trial in patients with progressive brain metastases (Alliance A071701).

About the speaker: Originally from Vancouver, BC, Dr. Priscilla Brastianos completed her medical school and internal medicine residency at Johns Hopkins School of Medicine and fellowship training in hematology/oncology and neuro-oncology at the Dana-Farber Cancer Institute and Massachusetts General Hospital. She is now director of the Central Nervous System Metastasis Center at Massachusetts General Hospital and leads a multi-R01-funded laboratory. Dr. Brastianos’ research focuses on understanding the genomic mechanisms that drive primary and metastatic brain tumors. She has lead studies which have identified novel therapeutic targets in brain tumors and she has translated her scientific findings to national multicenter trials. She also leads a multidisciplinary central nervous system metastasis clinic at Massachusetts General Hospital/Harvard Medical School. She has received a number of awards for her work including a ‘NextGen Star’ award by the American Association for Cancer Research, a Damon Runyon Clinical Investigator Award, a Breast Cancer Research Foundation Award, a Susan G. Komen Career Catalyst Award, the American Brain Tumor Association Joel Gingras Award and the Anne Klibanski Award for Excellence in Mentorship.