Tracking the Origins of Lung Cancer

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Science  15 Jul 2005:
Vol. 309, Issue 5733, pp. 357
DOI: 10.1126/science.309.5733.357a

Lung cancer is the leading cause of cancer deaths in the United States. Most patients are diagnosed at an advanced stage of the disease, which has hampered research into its molecular and cellular origins. Consequently, only 15% of patients who are diagnosed today with the most common subtype of lung cancer will survive for 5 years—a bleak statistic that has not changed over the past 15 years.

Two reports illustrate that there may be reasons for optimism, due largely to recent advances in how the disease is approached methodologically and conceptually. To identify genes that play a role in the pathogenesis of the distinct subtypes of lung cancer, Tonon et al. studied human tumors by comparative genomic hybridization and expression profiling, two methods that, when integrated, provide a comprehensive picture of the critical genomic alterations that characterize each subtype. Interestingly, adenocarcinomas and squamous cell carcinomas (SCCs), two subtypes previously thought to have diverse etiologies because of their distinct histopathological features, were found to have nearly identical genomic signatures, suggesting that they may in fact arise from a common stem/progenitor cell.

The possible stem cell origin of lung cancer was the focus of independent work by Kim et al. Using a mouse model, they identified a population of cells, termed BASCs (bronchioalveolar stem cells), whose anatomical location and ability to self-renew and differentiate into multiple lung cell types are features consistent with those predicted for a lung stem/progenitor cell. Remarkably, BASCs were enriched in early-stage lung tumors in mice, and they expanded in response to oncogenic stimuli in cell culture, suggesting that they might play a role in tumorigenesis. Should future studies identify BASC counterparts with a causal role in human lung cancer, this could lead to new therapies that target the earliest stage of disease, a development that is desperately needed. — PAK

Proc. Natl. Acad. Sci. U.S.A. 102, 9625 (2005); Cell 121, 823 (2005).


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