title: Targeted Therapy in Brain Metastases: Ready for Primetime?
abstract: Brain metastasis is a serious complication of cancer that causes significant morbidity for patients. Over the last decade, numerous new driver somatic mutations have been recognized and targeted therapies are changing the landscape of treatment in lung cancer, breast cancer, and melanoma, which are also the three most common cancers that result in brain metastases. The common actionable mutations include the EGFR mutation and anaplastic lymphoma kinase (ALK) translocations in non-small cell lung cancer, the HER2 mutation in breast cancer, and the BRAF mutation in melanoma. However, most of the early trials with targeted agents excluded patients with brain metastases. With a better understanding of the biology, several recent trials of targeted therapy that focus on brain metastases have been reported and others are ongoing. Novel agents with better penetration across the blood-brain barrier are currently being investigated for patients with brain metastases. In this review, we discuss the current state of use and future directions of targeted therapies in brain metastases.
authors.affiliation: From the Division of Hematology and Oncology, Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA; Burkhardt Brain Tumor and Neuro-Oncology Center, Department of Medicine, Neurologic Institute, Cleveland Clinic, Cleveland, OH; Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Vyshak A
authors.initials: VA
authors.lastname: Venur
authors.affiliation: From the Division of Hematology and Oncology, Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA; Burkhardt Brain Tumor and Neuro-Oncology Center, Department of Medicine, Neurologic Institute, Cleveland Clinic, Cleveland, OH; Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Manmeet S
authors.initials: MS
authors.lastname: Ahluwalia
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics; D058990:Molecular Targeted Therapy; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D048493:Proto-Oncogene Proteins B-raf; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; C000626173:ALK protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C482119:BRAF protein, human