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Review
. 2014 Jan;232(2):121-33.
doi: 10.1002/path.4275.

The evolving genomic classification of lung cancer

David S Shames  1 , Ignacio I Wistuba
Affiliations
Free PMC article
Review

The evolving genomic classification of lung cancer

David S Shames et al. J Pathol. 2014 Jan.
Free PMC article

Abstract

EGFR gene mutations and ALK gene fusions are well-characterized molecular targets in NSCLC. Activating alterations in a variety of potential oncogenic driver genes have also been identified in NSCLC, including ROS1, RET, MET, HER2, and BRAF. Together with EGFR and ALK, these mutations account for ∼20% of NSCLCs. The identification of these oncogenic drivers has led to the design of rationally targeted therapies that have produced superior clinical outcomes in tumours harbouring these mutations. Many patients, however, have de novo or acquired resistance to these therapies. In addition, most NSCLCs are genetically complex tumours harbouring multiple potential activating events. For these patients, disease subsets are likely to be defined by combination strategies involving a number of targeted agents. These targets include FGFR1, PTEN, MET, MEK, PD-1/PD-L1, and NaPi2b. In light of the myriad new biomarkers and targeted agents, multiplex testing strategies will be invaluable in identifying the appropriate patients for each therapy and enabling targeted agents to be channelled to the patients most likely to gain benefit. The challenge now is how best to interpret the results of these genomic tests, in the context of other clinical data, to optimize treatment choices in NSCLC.

Keywords: ALK; EGFR; NSCLC; biomarkers; genomic classification; lung cancer; molecular targets; monoclonal antibodies; multiplex testing; tyrosine-kinase inhibitors.

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Figures

Figure 1
Figure 1
Evolving genomic classification of NSCLC. Li T et al: J Clin Oncol 2013; 31: 1039–1049. Reprinted with permission. © 2013 by American Society of Clinical Oncology. All rights reserved .
Figure 2
Figure 2
Lung diagnostic testing today and in the future.
Figure 3
Figure 3
The future of oncology testing in NSCLC. BC, breast cancer; CTCs, circulating tumour cells; qRT, real-time reverse transcription; WGS, whole genome sequencing.
Figure 4
Figure 4
Hypothetical effect on OS/PFS in prognostic/predictive subsets and remaining ‘all-comer’ patients. Modified from ref 105.
See this image and copyright information in PMC

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