TY - JOUR
T1 - A translational view of the molecular pathogenesis of lung cancer
AU - Sato, Mitsuo
AU - Shames, David S.
AU - Gazdar, Adi F.
AU - Minna, John D.
N1 - Funding Information:
Disclosure: JDM has a research grant from Astra Zeneca to study their new drugs preclinically. The authors declare no other conflict of interest.
Funding Information:
This work was supported by Lung Cancer SPORE P50CA75907, NO1-CN-43301, DOD VITAL and PROSPECT grants, NASA/NSCOR (NNJ05HD36G), and the Gillson Longenbaugh Foundation.
PY - 2007/4
Y1 - 2007/4
N2 - Molecular genetic studies of lung cancer have revealed that clinically evident lung cancers have multiple genetic and epigenetic abnormalities, including DNA sequence alterations, copy number changes, and aberrant promoter hypermethylation. Together, these abnormalities result in the activation of oncogenes and inactivation of tumor-suppressor genes. In many cases these abnormalities can be found in premalignant lesions and in histologically normal lung bronchial epithelial cells. Findings suggest that lung cancer develops through a stepwise process from normal lung epithelial cells towards frank malignancy, which usually occurs as a result of cigarette smoking. Lung cancer has a high morbidity because it is difficult to detect early and is frequently resistant to available chemotherapy and radiotherapy. New, rationally designed early detection, chemoprevention, and therapeutic strategies based on the growing understanding of the molecular changes important to lung cancer are under investigation. For example, methylated tumor DNA sequences in sputum or blood are being investigated for early detection screening, and new treatments that specifically target molecules such as vascular endothelial growth factor and the epidermal growth factor receptor are becoming available. Meanwhile, global gene expression signatures from individual tumors are showing potential as prognostic and therapeutic indicators, such that molecular typing of individual tumors for therapy selection is not far away. Finally, the recent development of a model system of immortalized human bronchial epithelial cells, along with a paradigm shift in the conception of cancer stem cells, promises to improve the situation for patients with lung cancer. These advances highlight the translation of molecular discoveries on lung cancer pathogenesis from the laboratory to the clinic.
AB - Molecular genetic studies of lung cancer have revealed that clinically evident lung cancers have multiple genetic and epigenetic abnormalities, including DNA sequence alterations, copy number changes, and aberrant promoter hypermethylation. Together, these abnormalities result in the activation of oncogenes and inactivation of tumor-suppressor genes. In many cases these abnormalities can be found in premalignant lesions and in histologically normal lung bronchial epithelial cells. Findings suggest that lung cancer develops through a stepwise process from normal lung epithelial cells towards frank malignancy, which usually occurs as a result of cigarette smoking. Lung cancer has a high morbidity because it is difficult to detect early and is frequently resistant to available chemotherapy and radiotherapy. New, rationally designed early detection, chemoprevention, and therapeutic strategies based on the growing understanding of the molecular changes important to lung cancer are under investigation. For example, methylated tumor DNA sequences in sputum or blood are being investigated for early detection screening, and new treatments that specifically target molecules such as vascular endothelial growth factor and the epidermal growth factor receptor are becoming available. Meanwhile, global gene expression signatures from individual tumors are showing potential as prognostic and therapeutic indicators, such that molecular typing of individual tumors for therapy selection is not far away. Finally, the recent development of a model system of immortalized human bronchial epithelial cells, along with a paradigm shift in the conception of cancer stem cells, promises to improve the situation for patients with lung cancer. These advances highlight the translation of molecular discoveries on lung cancer pathogenesis from the laboratory to the clinic.
KW - Clinic
KW - Early detection
KW - Epidermal growth factor receptor
KW - Lung cancer
KW - Molecular pathogenesis
KW - Prevention
KW - Targeted therapy
KW - Tyrosine kinase inhibitor
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U2 - 10.1097/01.JTO.0000263718.69320.4c
DO - 10.1097/01.JTO.0000263718.69320.4c
M3 - Article
C2 - 17409807
AN - SCOPUS:34247891719
SN - 1556-0864
VL - 2
SP - 327
EP - 343
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
IS - 4
ER -