Lung Cancer.pdf

Prevention and Early Detection of Lung Cancer 261
In 1976, Sporn coined the term chemoprevention, which is defined as
the use of natural or synthetic chemical agents to reverse, suppress, or
prevent carcinogenic progression before the development of invasive cancer.
Chemoprevention uses knowledge gained from basic biological research
to design clinical interventions that attempt to halt the process of
carcinogenesis. Chemoprevention in the aerodigestive tract is predicated
on the concepts of field cancerization and the multistep model of carcinogenesis,
which are discussed in the section Model of Lung Cancer Development
earlier in this chapter.
Strategies targeting arrest or reversal of 1 or several of the steps in the
multistep process of carcinogenesis may impede the development of cancer.
This paradigm has been described particularly well in studies involving
cancers of the head and neck, which have focused on oral premalignant
lesions, including leukoplakia and erythroplakia, and their associated risk
of progression to cancer. Most of the potential chemopreventive agents
studied in lung cancer are agents that have first shown promise in the
chemoprevention of head and neck cancer.
This section will discuss general strategies of chemoprevention; agents
studied for their potential chemopreventive effect in aerodigestive tract
malignancies, including lung cancer; major lung cancer chemoprevention
trials undertaken to date; and potential new molecular targets for chemoprevention
strategies.
Strategies
Chemoprevention strategies target the carcinogenic process at early and
potentially reversible stages, focusing on inhibition of 1 or many steps in
the progression towards cancer. As a cell’s exposure to carcinogens increases,
genetic mutations and other processes occur that eventually lead
to excessive proliferation of genetically altered cells and, eventually, cancer.
Chemoprevention strategies include primary prevention in groups at
high risk, reversal of premalignant lesions, and prevention of second primary
tumors.
Primary Prevention in High-Risk Groups
At present, there is no standard way to determine which patients are at
high risk for the development of lung cancer. Chemoprevention trials
have studied patients who are believed to be at high risk for the development
of cancer. Specific factors used at present to define high risk include
a smoking history of 20 to 30 pack-years; a previous tobacco-related cancer,
including head and neck, lung, esophagus, or bladder cancer; and
sputum atypia. In the future, it may be possible to identify high-risk patients
through measurement of specific molecular markers (for more information,
see the section Potential New Molecular Targets later in this
chapter).