title: Treatment of brain metastases in the modern genomic era.
abstract: Development of brain metastasis (BM) portends a dismal prognosis for patients with cancer. Melanomas and carcinomas of the lung, breast, and kidney are the most common malignancies to metastasize to the brain. Recent advances in molecular genetics have enabled the identification of actionable, clinically relevant genetic alterations within primary tumors and their corresponding metastases. Adoption of genotype-guided treatment strategies for the management of systemic malignancy has resulted in dramatic and durable responses. Unfortunately, despite these therapeutic advances, central nervous system (CNS) relapses are not uncommon. Although these relapses have historically been attributed to limited blood brain barrier penetration of anti-neoplastic agents, recent work has demonstrated genetic heterogeneity such that metastatic sites, including BM, harbor relevant genetic alterations that are not present in primary tumor biopsies. This improved insight into molecular mechanisms underlying site specific recurrences can inform strategies for targeting these oncogenic drivers. Thus, development of rational, genomically guided CNS-penetrant therapies is crucial for ongoing therapeutic success.
authors: Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States; Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
authors: Ibiayi
authors: I
authors: Dagogo-Jack
authors: Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
authors: Corey M
authors: CM
authors: Gill
authors: Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
authors: Daniel P
authors: DP
authors: Cahill
authors: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
authors: Sandro
authors: S
authors: Santagata
authors: Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States; Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States. Electronic address: pbrastianos@mgh.harvard.edu.
authors: Priscilla K
authors: PK
authors: Brastianos
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D023281:Genomics / Q000379:methods*; D005838:Genotype; D006801:Humans; D058990:Molecular Targeted Therapy; D009364:Neoplasm Recurrence, Local; D011379:Prognosis
chemical_list: D000970:Antineoplastic Agents
keywords: Brain metastases; Genomics; Sequencing; Targeted therapies