Genotyping and genomic profiling of non-small-cell lung cancer: Implications for current and future therapies

T. Li, H.-J. Kung, P.C. Mack, D.R. Gandara

Research output: Contribution to journalArticle

276 Citations (Scopus)

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. © 2013 by American Society of Clinical Oncology.
Original languageEnglish
Pages (from-to)1039-1049
Number of pages11
JournalJournal of Clinical Oncology
Volume31
Issue number8
DOIs
Publication statusPublished - 2013
Externally publishedYes

Fingerprint

Non-Small Cell Lung Carcinoma
Neoplasms
Therapeutics
Technology
erbB-1 Genes
Gene Rearrangement
Standard of Care
Pharmaceutical Preparations
Protein-Tyrosine Kinases
Decision Making
Biomarkers
Genotype
Maintenance
Genome
Biopsy
Mutation

Keywords

  • afatinib
  • anaplastic lymphoma kinase
  • crizotinib
  • dacomitinib
  • epidermal growth factor receptor
  • erlotinib
  • gefitinib
  • lapatinib
  • protein tyrosine kinase inhibitor
  • trastuzumab
  • advanced cancer
  • cancer genetics
  • cancer growth
  • drug targeting
  • gain of function mutation
  • gene rearrangement
  • gene sequence
  • genetic association
  • human
  • lung non small cell cancer
  • medical decision making
  • molecular evolution
  • molecularly targeted therapy
  • patient care
  • priority journal
  • review
  • standard
  • Algorithms
  • Carcinoma, Non-Small-Cell Lung
  • DNA Mutational Analysis
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genes, Neoplasm
  • Genetic Testing
  • Genome, Human
  • Genotype
  • Humans
  • Individualized Medicine
  • Lung Neoplasms
  • Patient Selection
  • Tumor Markers, Biological

Cite this

Genotyping and genomic profiling of non-small-cell lung cancer: Implications for current and future therapies. / Li, T.; Kung, H.-J.; Mack, P.C.; Gandara, D.R.

In: Journal of Clinical Oncology, Vol. 31, No. 8, 2013, p. 1039-1049.

Research output: Contribution to journalArticle

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title = "Genotyping and genomic profiling of non-small-cell lung cancer: Implications for current and future therapies",
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. {\circledC} 2013 by American Society of Clinical Oncology.",
keywords = "afatinib, anaplastic lymphoma kinase, crizotinib, dacomitinib, epidermal growth factor receptor, erlotinib, gefitinib, lapatinib, protein tyrosine kinase inhibitor, trastuzumab, advanced cancer, cancer genetics, cancer growth, drug targeting, gain of function mutation, gene rearrangement, gene sequence, genetic association, human, lung non small cell cancer, medical decision making, molecular evolution, molecularly targeted therapy, patient care, priority journal, review, standard, Algorithms, Carcinoma, Non-Small-Cell Lung, DNA Mutational Analysis, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genes, Neoplasm, Genetic Testing, Genome, Human, Genotype, Humans, Individualized Medicine, Lung Neoplasms, Patient Selection, Tumor Markers, Biological",
author = "T. Li and H.-J. Kung and P.C. Mack and D.R. Gandara",
note = "引用次數:211 Export Date: 5 March 2018 CODEN: JCOND 通訊地址: Li, T.; University of California, Davis Comprehensive Cancer Center, Division of Hematology and Oncology, 4501 X St, Ste 3016, Sacramento, CA, United States; 電子郵件: tianhong.li@ucdmc.ucdavis.edu 化學物質/CAS: afatinib, 439081-18-2, 850140-72-6, 850140-73-7; anaplastic lymphoma kinase, 166433-56-3; crizotinib, 877399-52-5; dacomitinib, 1110813-31-4; epidermal growth factor receptor, 79079-06-4; erlotinib, 183319-69-9, 183321-74-6; gefitinib, 184475-35-2, 184475-55-6, 184475-56-7; lapatinib, 231277-92-2, 388082-78-8, 437755-78-7; trastuzumab, 180288-69-1; Tumor Markers, Biological 參考文獻: Siegel, R., DeSantis, C., Virgo, K., Cancer treatment and survivorship statistics, 2012 (2012) CA Cancer J Clin, 62, pp. 220-241; Larsen, J.E., Minna, J.D., Molecular biology of lung cancer: Clinical implications (2011) Clin Chest Med, 32, pp. 703-740; Sun, S., Schiller, J.H., Spinola, M., Minna, J.D., New molecularly targeted therapies for lung cancer (2007) Journal of Clinical Investigation, 117 (10), pp. 2740-2750. , http://www.jci.org/cgi/reprint/117/10/2740, DOI 10.1172/JCI31809; Ding, L., Getz, G., Wheeler, D.A., Somatic mutations affect key pathways in lung adenocarcinoma (2008) Nature, 455, pp. 1069-1075; Pao, W., Girard, N., New driver mutations in non-small-cell lung cancer (2011) Lancet Oncol, 12, pp. 175-180; Gandara, D.R., Mack, P.C., Li, T., Evolving treatment algorithms for advanced non-small-cell lung cancer: 2009 looking toward 2012 (2009) Clin Lung Cancer, 10, pp. 392-394; Gandara, D.R., Li, T., Lara Jr., P.N., Algorithm for codevelopment of new drug-predictive biomarker combinations: Accounting for inter-and intrapatient tumor heterogeneity (2012) Clin Lung Cancer, 13, pp. 321-325; Mok, T.S., Wu, Y.L., Thongprasert, S., Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma (2009) N Engl J Med, 361, pp. 947-957; Mitsudomi, T., Morita, S., Yatabe, Y., Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): An open label randomised phase 3 trial (2010) Lancet Oncol, 11, pp. 121-128; Maemondo, M., Inoue, A., Kobayashi, K., Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR (2010) N Engl J Med, 362, pp. 2380-2388; Zhou, C., Wu, Y.L., Chen, G., Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-smallcell lung cancer (OPTIMAL CTONG-0802): A multicentre open-label randomised phase 3 study (2011) Lancet Oncol, 12, pp. 735-742; Rosell, R., Carcereny, E., Gervais, R., Erlotinib versus standard chemotherapy as first-line treatment for european patients with advanced EGFR mutationpositive non-small-cell lung cancer (EURTAC): A multicentre open-label randomised phase 3 trial (2012) Lancet Oncol, 13, pp. 239-246; Kwak, E.L., Bang, Y.J., Camidge, D.R., Anaplastic lymphoma kinase inhibition in nonsmall-cell lung cancer (2010) N Engl J Med, 363, pp. 1693-1703; http://www.accessdata.fda.gov/drugsatfda-docs/appletter/2011/ 202570s000ltr.pdf, US Food and Drug Administration: FDA approves Xalkori with companion diagnostic for a type of late-state lung cancer; 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year = "2013",
doi = "10.1200/JCO.2012.45.3753",
language = "English",
volume = "31",
pages = "1039--1049",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
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TY - JOUR

T1 - Genotyping and genomic profiling of non-small-cell lung cancer: Implications for current and future therapies

AU - Li, T.

AU - Kung, H.-J.

AU - Mack, P.C.

AU - Gandara, D.R.

N1 - 引用次數:211 Export Date: 5 March 2018 CODEN: JCOND 通訊地址: Li, T.; University of California, Davis Comprehensive Cancer Center, Division of Hematology and Oncology, 4501 X St, Ste 3016, Sacramento, CA, United States; 電子郵件: tianhong.li@ucdmc.ucdavis.edu 化學物質/CAS: afatinib, 439081-18-2, 850140-72-6, 850140-73-7; anaplastic lymphoma kinase, 166433-56-3; crizotinib, 877399-52-5; dacomitinib, 1110813-31-4; epidermal growth factor receptor, 79079-06-4; erlotinib, 183319-69-9, 183321-74-6; gefitinib, 184475-35-2, 184475-55-6, 184475-56-7; lapatinib, 231277-92-2, 388082-78-8, 437755-78-7; trastuzumab, 180288-69-1; Tumor Markers, Biological 參考文獻: Siegel, R., DeSantis, C., Virgo, K., Cancer treatment and survivorship statistics, 2012 (2012) CA Cancer J Clin, 62, pp. 220-241; Larsen, J.E., Minna, J.D., Molecular biology of lung cancer: Clinical implications (2011) Clin Chest Med, 32, pp. 703-740; Sun, S., Schiller, J.H., Spinola, M., Minna, J.D., New molecularly targeted therapies for lung cancer (2007) Journal of Clinical Investigation, 117 (10), pp. 2740-2750. , http://www.jci.org/cgi/reprint/117/10/2740, DOI 10.1172/JCI31809; Ding, L., Getz, G., Wheeler, D.A., Somatic mutations affect key pathways in lung adenocarcinoma (2008) Nature, 455, pp. 1069-1075; Pao, W., Girard, N., New driver mutations in non-small-cell lung cancer (2011) Lancet Oncol, 12, pp. 175-180; Gandara, D.R., Mack, P.C., Li, T., Evolving treatment algorithms for advanced non-small-cell lung cancer: 2009 looking toward 2012 (2009) Clin Lung Cancer, 10, pp. 392-394; Gandara, D.R., Li, T., Lara Jr., P.N., Algorithm for codevelopment of new drug-predictive biomarker combinations: Accounting for inter-and intrapatient tumor heterogeneity (2012) Clin Lung Cancer, 13, pp. 321-325; Mok, T.S., Wu, Y.L., Thongprasert, S., Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma (2009) N Engl J Med, 361, pp. 947-957; Mitsudomi, T., Morita, S., Yatabe, Y., Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): An open label randomised phase 3 trial (2010) Lancet Oncol, 11, pp. 121-128; Maemondo, M., Inoue, A., Kobayashi, K., Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR (2010) N Engl J Med, 362, pp. 2380-2388; Zhou, C., Wu, Y.L., Chen, G., Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-smallcell lung cancer (OPTIMAL CTONG-0802): A multicentre open-label randomised phase 3 study (2011) Lancet Oncol, 12, pp. 735-742; Rosell, R., Carcereny, E., Gervais, R., Erlotinib versus standard chemotherapy as first-line treatment for european patients with advanced EGFR mutationpositive non-small-cell lung cancer (EURTAC): A multicentre open-label randomised phase 3 trial (2012) Lancet Oncol, 13, pp. 239-246; Kwak, E.L., Bang, Y.J., Camidge, D.R., Anaplastic lymphoma kinase inhibition in nonsmall-cell lung cancer (2010) N Engl J Med, 363, pp. 1693-1703; http://www.accessdata.fda.gov/drugsatfda-docs/appletter/2011/ 202570s000ltr.pdf, US Food and Drug Administration: FDA approves Xalkori with companion diagnostic for a type of late-state lung cancer; 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PY - 2013

Y1 - 2013

N2 - 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. © 2013 by American Society of Clinical Oncology.

AB - 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. © 2013 by American Society of Clinical Oncology.

KW - afatinib

KW - anaplastic lymphoma kinase

KW - crizotinib

KW - dacomitinib

KW - epidermal growth factor receptor

KW - erlotinib

KW - gefitinib

KW - lapatinib

KW - protein tyrosine kinase inhibitor

KW - trastuzumab

KW - advanced cancer

KW - cancer genetics

KW - cancer growth

KW - drug targeting

KW - gain of function mutation

KW - gene rearrangement

KW - gene sequence

KW - genetic association

KW - human

KW - lung non small cell cancer

KW - medical decision making

KW - molecular evolution

KW - molecularly targeted therapy

KW - patient care

KW - priority journal

KW - review

KW - standard

KW - Algorithms

KW - Carcinoma, Non-Small-Cell Lung

KW - DNA Mutational Analysis

KW - Gene Expression Profiling

KW - Gene Expression Regulation, Neoplastic

KW - Genes, Neoplasm

KW - Genetic Testing

KW - Genome, Human

KW - Genotype

KW - Humans

KW - Individualized Medicine

KW - Lung Neoplasms

KW - Patient Selection

KW - Tumor Markers, Biological

U2 - 10.1200/JCO.2012.45.3753

DO - 10.1200/JCO.2012.45.3753

M3 - Article

VL - 31

SP - 1039

EP - 1049

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 8

ER -