Patrick R Halliday1,2, Collin M Blakely1,2, Trever G Bivona3,4. 1. Department of Medicine, Division of Hematology and Oncology, University of California, San Francisco, San Francisco, CA, USA. 2. Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, 600 16th Street, N212D, San Francisco, CA, 94158, USA. 3. Department of Medicine, Division of Hematology and Oncology, University of California, San Francisco, San Francisco, CA, USA. trever.bivona@ucsf.edu. 4. Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, 600 16th Street, N212D, San Francisco, CA, 94158, USA. trever.bivona@ucsf.edu.
Abstract
PURPOSE OF REVIEW: Lung cancer remains the leading cause of cancer-related mortality worldwide. Genetic and molecular profiling of non-small cell lung cancer (NSCLC) has led to the discovery of actionable oncogenic driver alterations, which has revolutionized treatment for this disease. This review will move beyond traditional mutational drivers such as EGFR and ALK and will instead focus on emerging targets and the efficacy of new precision therapies. RECENT FINDINGS: Here, we discuss both established and emerging targeted therapy approaches, as well as ongoing challenges for the treatment of NSCLC patients harboring oncogenic alterations of the following types-gene fusions (ROS1, RET, NTRK), receptor tyrosine kinases (MET amplification and exon 14 mutations and EGFR/HER2 exon 20 insertion mutations), and MAPK signaling (SHP2 and altered BRAF and NF1). The treatment of lung cancer is increasingly biomarker-driven, as patients are selected for targeted agents based on the identification of genetic alterations amenable to inhibition. Our ability to further improve patient outcomes with this precision medicine approach will require continued efforts to identify, characterize, and target lesions driving lung cancer tumorigenesis and progression.
PURPOSE OF REVIEW: Lung cancer remains the leading cause of cancer-related mortality worldwide. Genetic and molecular profiling of non-small cell lung cancer (NSCLC) has led to the discovery of actionable oncogenic driver alterations, which has revolutionized treatment for this disease. This review will move beyond traditional mutational drivers such as EGFR and ALK and will instead focus on emerging targets and the efficacy of new precision therapies. RECENT FINDINGS: Here, we discuss both established and emerging targeted therapy approaches, as well as ongoing challenges for the treatment of NSCLCpatients harboring oncogenic alterations of the following types-gene fusions (ROS1, RET, NTRK), receptor tyrosine kinases (MET amplification and exon 14 mutations and EGFR/HER2 exon 20 insertion mutations), and MAPK signaling (SHP2 and altered BRAF and NF1). The treatment of lung cancer is increasingly biomarker-driven, as patients are selected for targeted agents based on the identification of genetic alterations amenable to inhibition. Our ability to further improve patient outcomes with this precision medicine approach will require continued efforts to identify, characterize, and target lesions driving lung cancer tumorigenesis and progression.
Authors: Victoria Sarne; Samuel Huter; Sandrina Braunmueller; Lisa Rakob; Nico Jacobi; Melitta Kitzwögerer; Christoph Wiesner; Peter Obrist; Rita Seeboeck Journal: Int J Mol Sci Date: 2020-06-28 Impact factor: 5.923