Genotyping and Genomic Profiling of Non–Small-Cell Lung Cancer: Implications for Current and Future Therapies
Publication: Journal of Clinical Oncology
Abstract
Substantial advances have been made in understanding critical molecular and cellular mechanisms driving tumor initiation, maintenance, and progression in non–small-cell lung cancer (NSCLC). Over the last decade, these findings have led to the discovery of a variety of novel drug targets and the development of new treatment strategies. Already, the standard of care for patients with advanced-stage NSCLC is shifting from selecting therapy empirically based on a patient's clinicopathologic features to using biomarker-driven treatment algorithms based on the molecular profile of a patient's tumor. This approach is currently best exemplified by treating patients with NSCLC with first-line tyrosine kinase inhibitors when their cancers harbor gain-of-function hotspot mutations in the epidermal growth factor receptor (EGFR) gene or anaplastic lymphoma kinase (ALK) gene rearrangements. These genotype-based targeted therapies represent the first step toward personalizing NSCLC therapy. Recent technology advances in multiplex genotyping and high-throughput genomic profiling by next-generation sequencing technologies now offer the possibility of rapidly and comprehensively interrogating the cancer genome of individual patients from small tumor biopsies. This advance provides the basis for categorizing molecular-defined subsets of patients with NSCLC in whom a growing list of novel molecularly targeted therapeutics are clinically evaluable and additional novel drug targets can be discovered. Increasingly, practicing oncologists are facing the challenge of determining how to select, interpret, and apply these new genetic and genomic assays. This review summarizes the evolution, early success, current status, challenges, and opportunities for clinical application of genotyping and genomic tests in therapeutic decision making for NSCLC.
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Authors' Disclosures of Potential Conflicts of Interest
Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a “U” are those for which no compensation was received; those relationships marked with a “C” were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.
Employment or Leadership Position: None Consultant or Advisory Role: Tianhong Li, Astellas (C), Genentech (C), Daiichi Sankyo (C); Philip C. Mack, Boehringer Ingelheim (C); David R. Gandara, Caris Life Sciences (C), Response Genetics (C) Stock Ownership: None Honoraria: Philip C. Mack, Boehringer Ingelheim Research Funding: Tianhong Li, Astellas, Eli Lilly Expert Testimony: None Other Remuneration: None
Information & Authors
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© 2013 by American Society of Clinical Oncology.
History
Published online: February 11, 2013
Published in print: March 10, 2013
Authors
Author Contributions
Conception and design: All authors
Data analysis and interpretation: Tianhong Li, Philip C. Mack, David R. Gandara
Manuscript writing: All authors
Final approval of manuscript: All authors
Funding Information
T.L. is supported by Grant No. UL1 RR024146 from the National Center for Research Resources; University of California Davis Comprehensive Cancer Center Developmental Award (National Institutes of Health/National Cancer Institute Grant No. P30CA093373); a research fund from the Division of Hematology and Oncology, Department of Internal Medicine, School of Medicine, University of California Davis; and the Hope Foundation (Southwest Oncology Group Young Investigator Award).
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Article Citation
Genotyping and Genomic Profiling of Non–Small-Cell Lung Cancer: Implications for Current and Future Therapies. JCO 31, 1039-1049(2013).
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Journal of Clinical Oncology 2013 31:8, 1039-1049
Journal of Clinical Oncology 2013 31:8, 1039-1049
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