Genetics and Molecular Biology of Lung Cancer
Molecular Biology of Specific Diseases
Published Online: 15 SEP 2006
Copyright © 2006 Wiley-VCH Verlag GmbH & Co. KGaA. All rights reserved.
Reviews in Cell Biology and Molecular Medicine
How to Cite
Roth, J. A. 2006. Genetics and Molecular Biology of Lung Cancer. Reviews in Cell Biology and Molecular Medicine. .
- Published Online: 15 SEP 2006
Lung cancer is a paradigm of carcinogen-induced human cancer. It is estimated that for every 3 million cigarettes purchased, a lung cancer follows 35 years later. Although the majority of lung cancers occurs in men, the incidence in women is rising rapidly in some regions.
Epidemiologic studies have irrefutably linked cigarette smoking and human lung cancer as well as other etiologic agents such as asbestos and radon. However, the molecular events within the cell that culminate in the development and progression of human lung cancer remain poorly understood. This is an important area for future research for several reasons. Elucidation of the molecular events in the genesis of lung cancer may have relevance to mechanisms for other carcinogen-induced tumors. Prevention, early diagnosis, and treatment strategies will be more rationally designed if they are based on molecular mechanisms.
The observation that genes responsible for carcinogenesis were altered forms of genes normally present in eukaryotic cells initiated many of the advances in molecular biology that have increased our understanding of lung carcinogenesis at the molecular level. Many of these genes have been implicated in the development of human cancer. An understanding of the molecular basis for lung carcinogenesis is essential for the development of improved methods of diagnosis, staging, treatment, and prevention for lung cancer.
The cell of origin for lung cancers is controversial. All histologies for non–small-cell lung cancer (NSCLC) have phenotypic features of the differentiated cell types in normal or injured bronchial epithelium. Small-cell lung cancer (SCLC) cells have neuroendocrine markers including high levels of the polypeptide hormones gastrin-releasing peptide and calcitonin, creatine kinase isoenzyme BB, L-dopa decarboxylase, and neuron-specific enolase. Endocrine cells can be found in normal bronchial mucosa. Thus, one possibility is that each of the four major histologies arises from alterations in its preexisting normal counterpart.
An alternative hypothesis is that the four types of lung cancer arise from a common stem cell and are related through a common differentiation pathway of the normal bronchial epithelium. This is supported by the clinical observation that SCLC tumors can contain mixtures of SCLC and non-SCLC histologies. These transitions have been observed in vitro following insertion of the appropriate oncogene. For example, insertion of a mutated H-ras oncogene in SCLC cells with overexpression of c-myc causes transition to the large-cell undifferentiated phenotype.
- Non–small-cell Lung Cancers;
- Small-cell Lung Cancer;
- Tumor Suppressor Gene