Molecular Screening for Lung Cancer on the Way

 

Through the looking glass: Registered nurse Anita Broxson (left), Dr. Waun Ki Hong and Dr. Li Mao examine genetic abnormalities in lung cells using a technique called polymerase chain reaction (PCR)-based nucleotide acid analysis.

 

 

A molecular test that could detect the presence of lung cancer through blood and sputum samples may someday be used to screen for the disease.

 

Currently, there isn't a practical or definitive screening method for lung cancer, a disease that affects more than 170,000 people each year. Cigarette smoking and exposure to other environmental carcinogens are the primary causes of lung cancer.

 

While chest X-rays can pick up cancerous lesions, it has not been recommended as a routine annual screening tool because it often detects the disease late -- a time when cure is difficult to achieve.

 

"By the time lung cancer is large enough to be visible on a chest X-ray, it is far advanced and may have already metastasized to other parts of the body," says Dr. Waun Ki Hong, professor and chairman of the Department of Thoracic/Head and Neck Medical Oncology at M. D. Anderson. "For that reason, it is important that we find new methods of early detection and diagnosis."

 

Developing such a method is the subject of intensive study, Dr. Hong says, but there are many challenges which must be overcome first. The main challenge is to understand why some people -- particularly smokers and former smokers -- develop lung cancer, and others do not.

 

"Only a small percentage of people who smoke will ever develop lung cancer. This is because the disease is the result of a complex set of interactions between environmental factors -- such as smoking -- and the genetic makeup of the individual," explains Dr. Hong, holder of the Charles A. LeMaistre Distinguished Chair in Thoracic Oncology, given by W. A. "Tex" and Deborah Moncrief, Jr.

 

There are genes controlling enzymes that aid in metabolizing and detoxifying carcinogens. When a person smokes, Dr. Hong says, they inhale thousands of toxic substances, and these carcinogens are supposed to be metabolized, detoxified and excreted from the body as non-harmful substances.

 

If detoxifying enzymes are missing, however, tobacco carcinogens accumulate in the liver and blood over time and, subsequently, cause DNA damage. As a result, a person's risk of developing lung cancer -- and several other smoking-related cancers such as bladder, stomach and pancreas -- is increased.

 

Although one might think screening for the presence or absence of these enzymes would be beneficial in determining risk, "they actually would be of little use in the general population because they are associated with only slighly increased risks for lung cancer, Dr. Hong says. "Therefore, an even more targeted approach to detect lung cancer is needed."

 

According to Dr. Hong, identifying a cohort of individuals at risk is the first step to successfully developing an effective screening test for the disease. Dr. Margaret R. Spitz, chair of the Department of Epidemiology and holder of the Olga Keith Wiess Chair for Cancer Research, and her team are conducting cutting-edge molecular epidemiologic work in an effort to develop a lung cancer risk model.

 

Once a model is established and high-risk individuals can be identified, researchers can identify genetic or molecular abnormalities in bronchial epithelium. Through their ongoing work in detecting pre-cancerous manifestations in biopsied bronchial cells, Dr. Hong and his colleagues hope to eventually be able to detect the early warning signs of lung cancer through sputum analysis and possibly with a blood sample.

 

The implications of this research are tremendous for both cancer prevention, early detection and treatment, according to Dr. Hong, who also is an American Cancer Society Clinical Research Professor. "Since lung cancer patients often do not experience any symptoms of the disease until their cancer is well advanced, a routine screening test for smokers and for all adults over a certain age would allow us to diagnose and treat cancers at much earlier stages. This would offer many more patients real hope for a long-term cure.

 

"Equally exciting," he continues, "is the fact that this new technology also has the potential to diagnose patients who are at risk for lung cancer, but who have not yet developed the disease. Ideally, this will allow us to target patients for preventive therapy and head off their cancer before it ever occurs."

 

Dr. Hong believes molecular screening for lung cancer will be part of a routine physical check-up within the next 10 years.

 

Anyone wanting more information about this research and/or to participate in a lung cancer prevention study, call registered nurse Anita Broxson at (713) 745-2784.

Return to Spring 98