Lung Cancer.pdf

290 W.N. Hittelman, J.M. Kurie, and S.G. Swisher
Monitoring of Response to Chemopreventive Interventions
Current studies at M.D. Anderson are focusing on the questions whether
the frequency of clonal outgrowths is related to the risk of developing
lung cancer and whether effective chemopreventive strategies can reduce
the size and frequency of clonal outgrowths in the lungs. The answers to
these questions will be critical to the efficiency of future chemoprevention
trials that attempt to identify potentially efficacious agents.
The use of validated, quantifiable, intermediate molecular end points
may permit the identification of high-risk individuals who might best
benefit from chemopreventive intervention. Focusing on the individuals
at highest risk could reduce the number of participants and the duration
of clinical follow-up required in chemoprevention trials. The use of molecular
end points would also permit rapid determination of whether a
particular chemopreventive approach is having a positive impact on the
target tissue.
Early Detection
There is increasing interest being placed on detecting lung cancer at an
early stage when the tumor burden is low. The finding that spiral CT examinations
of the lung can detect very small abnormalities has led to the
hope that this approach could provide a physical method for early detection.
However, the clinical importance of these small lesions is uncertain
since their natural history is poorly understood. In some cases, these visualized
lesions, when biopsied, have turned out to be unrelated processes.
In other cases, these lesions have proven to be cancerous, but it is
not clear that the lesion would ever have progressed to a clinically important
lesion in the individual’s lifetime had the lesion not been removed.
Comparisons of molecular changes in these specimens obtained
following spiral CT to those found in specimens of later-stage disease
might provide useful information regarding the expected natural history
of these small lesions. In the long run, knowledge of the molecular
changes associated with lung cancer development may lead to the development
of reagents and targets for functional imaging studies that may
predict the future behavior of small lung lesions without a requirement
for biopsy.
Potential Noninvasive Methods of Assessing Molecular Changes
One of the problems with current molecular risk assessment and early detection
technologies is the requirement for relatively invasive endobronchial
or transthoracic biopsies to obtain lung tissue for molecular
analysis. For this reason, there is increased interest in determining
whether molecular assessment of exfoliated lung cells (e.g., in bronchial
washings or sputum) or surrogate epithelial tissues (e.g., oral epithelial
scrapings) might provide information about lung cancer risk.