Research ArticleCancer

Airway PI3K Pathway Activation Is an Early and Reversible Event in Lung Cancer Development

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Science Translational Medicine  07 Apr 2010:
Vol. 2, Issue 26, pp. 26ra25
DOI: 10.1126/scitranslmed.3000251

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An Ounce of Prevention for Lung Cancer

Lung cancer takes a terrific toll on humankind. Despite our understanding of the contribution of tobacco smoke, this knowledge has not been able to reverse the global increase in lung cancer incidence. New approaches are needed. Is there a way to tell whether a smoker will develop cancer and, even more important, can we see when this process starts so we can stop it? Work from Gustafson and colleagues has defined a biochemical harbinger of cancer in seemingly normal respiratory tissue that can be reversed before cancer begins.

Numerous cellular signaling pathways are deregulated in cancers, such as the Ras, p53, and phosphatidylinositol 3-kinase (PI3K) pathways. A molecular understanding of lung cancer may help to develop effective drugs for deterrence. To see whether they could find a predictor of impending cancer, the authors examined normal respiratory tract tissue from smokers with lung cancer or other abnormalities. By looking for previously determined gene expression signatures for various signaling pathways, they found that one of these pathways—PI3K—was clearly activated above normal values. Moreover, the PI3K pathway was already turned on in smokers with abnormal dysplastic lesions, precursors to lung cancer. Lung cancer cells themselves showed even higher expression of the genes in the PI3K pathway. Concluding that elevated PI3K pathway activity precedes the development of lung cancer, the authors assessed gene expression in tissue from patients with dysplasias who had been successfully treated with myo-inositol, an inhibitor of PI3K, finding effective down-regulation of the PI3K pathway.

Treatment of cancers with surgery, radiation, and chemotherapy—or, in some cases, targeted molecular therapies—may be the standard of care at present. But prevention should surely be the ultimate goal. The new tool reported in this article—measurement of PI3K pathway activation—and the demonstration that this is an early and reversible step in lung tumorigenesis are hopeful signs.


  • * These authors contributed equally to this work.

  • Citation: A. M. Gustafson, R. Soldi, C. Anderlind, M. B. Scholand, J. Qian, X. Zhang, K. Cooper, D. Walker, A. McWilliams, G. Liu, E. Szabo, J. Brody, P. P. Massion, M. E. Lenburg, S. Lam, A. H. Bild, A. Spira, Airway PI3K pathway activation is an early and reversible event in lung cancer development. Sci. Transl. Med. 2, 26ra25 (2010).

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