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Title: Emerging Gene Fusion Drivers in Primary and Metastatic Central Nervous System Malignancies: A Review of Available Evidence for Systemic Targeted Therapies.
Austin Authors: Brastianos, Priscilla K;Ippen, Franziska Maria;Hafeez, Umbreen ;Gan, Hui K 
Affiliation: Department of Hematology and Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
Department of Medical Oncology, Austin Health, Heidelberg, Victoria, Australia
Austin Health Clinical School of Nursing, La Trobe University, Heidelberg, Victoria, Australia
Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Issue Date: 2018
Date: 2018-04-27
Publication information: The oncologist 2018; 23(9): 1063-1075
Abstract: Primary and metastatic tumors of the central nervous system present a difficult clinical challenge, and they are a common cause of disease progression and death. For most patients, treatment consists primarily of surgery and/or radiotherapy. In recent years, systemic therapies have become available or are under investigation for patients whose tumors are driven by specific genetic alterations, and some of these targeted treatments have been associated with dramatic improvements in extracranial and intracranial disease control and survival. However, the success of other systemic therapies has been hindered by inadequate penetration of the drug into the brain parenchyma. Advances in molecular characterization of oncogenic drivers have led to the identification of new gene fusions driving oncogenesis in some of the most common sources of intracranial tumors. Systemic therapies targeting many of these alterations have been approved recently or are in clinical development, and the ability to penetrate the blood-brain barrier is now widely recognized as an important property of such drugs. We review this rapidly advancing field with a focus on recently uncovered gene fusions and brain-penetrant systemic therapies targeting them. Driver gene fusions involving receptor tyrosine kinases have been identified across a wide range of tumor types, including primary central nervous system (CNS) tumors and extracranial solid tumors that are associated with high rates of metastasis to the CNS (e.g., lung, breast, melanoma). This review discusses the systemic therapies that target emerging gene fusions, with a focus on brain-penetrant agents that will target the intracranial disease and, where present, also extracranial disease.
DOI: 10.1634/theoncologist.2017-0614
Journal: The oncologist
PubMed URL: 29703764
Type: Journal Article
Subjects: Brain metastasis
Gene rearrangement
Non‐small cell lung cancer
Primary brain tumor
Appears in Collections:Journal articles

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