Molecular Carcinogenesis and Chemoprevention of Lung Cancer

Lung cancer is by far the leading cause of cancer-related death,
worldwide and in the United States. 1 Despite substantial progress
in the treatment of lung cancer, which correlates with improvements
in surgery, radiation oncology, and chemotherapy,
5-year survival has improved from 7% to only 16% over the
last 2 decades. Although median survival in all stages of disease
has improved somewhat, the low likelihood of obtaining a cure
even with optimal modern therapy is largely because of the
clinical presentation of this disease in its advanced stages The
late diagnosis is almost certainly related to a covert carcinogenesis
phase that often evolves over 10 to 20 years and requires
multiple molecular genetic changes to facilitate the development
of invasive lung cancer. 2,3 Thus, there exists a strong rationale
for intervening in those stages of lung carcinogenesis
that could result in arrest or delay of disease progression to the
stage of frank cancer. Therefore, the strategies that are likely to
be successful will likely optimally target both better biological
understanding of lung cancer–mediated field carcinogenesis,
and the development of reliable biomarkers that can accurately
assess the likelihood of efficacy and toxicity across target
populations. Ultimately, strategies involving screening and
early detection, biomarker-based chemoprevention, smoking
cessation, and better biological understanding of the phenomenon
of lung carcinogenesis are all likely to be coupled with
individualized risk stratification in the development of modern
approaches to prevent this dreaded disease and reduce the societal
burden of lung cancer.