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Importance of molecular features of non-small cell lung cancer for choice of treatment.

ABSTRACT: Lung cancer is the leading cause of cancer-related deaths in the United States. Approximately 85% of lung cancer is categorized as non-small cell lung cancer, and traditionally, non-small cell lung cancer has been treated with surgery, radiation, and chemotherapy. Targeted agents that inhibit the epidermal growth factor receptor pathway have been developed and integrated into the treatment regimens in non-small cell lung cancer. Currently, approved epidermal growth factor receptor inhibitors include the tyrosine kinase inhibitors erlotinib and gefitinib. Molecular determinants, such as epidermal growth factor receptor-activating mutations, have been associated with response to epidermal growth factor receptor tyrosine kinase inhibitors and may be used to guide treatment choices in patients with non-small cell lung cancer. Thus, treatment choice for patients with non-small cell lung cancer depends on molecular features of tumors; however, improved techniques are required to increase the specificity and efficiency of molecular profiling so that these methods can be incorporated into routine clinical practice. This review provides an overview of how genetic analysis is currently used to direct treatment choices in non-small cell lung cancer.

SUBMITTER: Moran C

PROVIDER: S-EPMC3081153 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Importance of molecular features of non-small cell lung cancer for choice of treatment.

Moran Cesar C

The American journal of pathology 20110501 5

Lung cancer is the leading cause of cancer-related deaths in the United States. Approximately 85% of lung cancer is categorized as non-small cell lung cancer, and traditionally, non-small cell lung cancer has been treated with surgery, radiation, and chemotherapy. Targeted agents that inhibit the epidermal growth factor receptor pathway have been developed and integrated into the treatment regimens in non-small cell lung cancer. Currently, approved epidermal growth factor receptor inhibitors inc ...[more]

PMID: 21514411

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Project description:Current paradigms hold that lung carcinomas arise from pleuripotent stem cells capable of differentiation into one or several histological types. These paradigms suggest lung tumor cell ontogeny is determined by consequences of gene expression that recapitulate events important in embryonic lung development. Using oligonucleotide microarrays, we acquired gene profiles from 32 microdissected non-small-cell lung tumors. We determined the 100 top-ranked marker genes for adenocarcinoma, squamous cell, large cell, and carcinoid using nearest neighbor analysis. Results were validated by immunostaining for 11 selected proteins using a tissue microarray representing 80 tumors. Gene expression data of lung development were accessed from a publicly available dataset generated with the murine Mu11k genome microarray. Self-organized mapping identified two temporally distinct clusters of murine orthologues. Supervised clustering of lung development data showed large-cell carcinoma gene orthologues were in a cluster expressed in pseudoglandular and canalicular stages whereas adenocarcinoma homologues were predominantly in a cluster expressed later in the terminal sac and alveolar stages of murine lung development. Representative large-cell genes (E2F3, MYBL2, HDAC2, CDK4, PCNA) are expressed in the nucleus and are associated with cell cycle and proliferation. In contrast, adenocarcinoma genes are associated with lung-specific transcription pathways (SFTPB, TTF-1), cell adhesion, and signal transduction. In sum, non-small-cell lung tumors histology gene profiles suggest mechanisms relevant to ontogeny and clinical course. Adenocarcinoma genes are associated with differentiation and glandular formation whereas large-cell genes are associated with proliferation and differentiation arrest. The identification of developmentally regulated pathways active in tumorigenesis provides insights into lung carcinogenesis and suggests early steps may differ according to the eventual tumor morphology.

Dataset Information

Importance of molecular features of non-small cell lung cancer for choice of treatment.

Publications

Importance of molecular features of non-small cell lung cancer for choice of treatment.

Similar Datasets

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