Prepared September 2010 
Each year in the US, >200,000 new cases of lung cancer are diagnosed leading to 
>150,000 deaths.  The incidence of lung cancer in men has decreased significantly 
during the past 20 years while in women, the rate is finally approaching a plateau 
after a long period of increase.  Despite advance in early detection and treatment, 
lung cancer is often diagnosed at an advanced stage which carries a poor prognosis.  Almost 90% of 
lung cancer is related to smoking and in recent years, the use of tobacco has declined substantially in 
the US population giving us great hope for a future decline in the number of people that will face this 
disease. 

WHAT CAUSES LUNG CANCER

o There are two main types of lung cancer: small cell lung cancer (SCLC) found in 10-15% 
of cases and non-small cell lung cancer (NSCLC) found in 85-90% of cases. 
o Both prognosis and patient management are different for small cell versus non-small cell 
lung cancer. 
o As we all know, the major risk factor for the development of lung cancer is smoking and 
80-90% of the cases occur in association with smoking; in part due to the slow development 
of many forms of lung cancer, some estimate that nearly 60% of new cases occur in people 
that have either never smoked or quit many years ago. 
o 1 in 5 women with lung cancer have never smoked compared to 1 in 10 among men. 
o Other risk factors include genetics, and exposure to environmental carcinogens including 
asbestos and radon.   
o Loss of part of chromosome 3 and mutations in the Ras oncogene are among the earliest 
genetic changes observed in the development of lung cancer; other genes commonly 
mutated in lung cancer include p53, LKB1, and EGFR (the target of erlotinib and 
cetuximab). 
o Nitrosamines are one of the most potent lung carcinogens in tobacco, and have been shown 
damage DNA, and induce patterns of mutations in the p53 and Ras genes similar to those 
seen in human lung cancer. 
There is still much that we do not understand about lung cancer.  Thus, ACS continues to invest in a 
significant proportion of the lung cancer dollars on the causes of lung cancer at the molecular, 
genetic, and cellular level both with and without an association with smoking.  We currently fund 19
different projects costing >.7M focused on the origins of lung cancer.  In addition to those projects, 
we fund quite a few others which have small component which address biological issues relevant to 
lung cancer. 
One of the most exciting concepts in cancer biology today focuses on the idea that spread and/or 
recurrence of cancer is fueled by the presence of a small, residual population of cancer stem cells 
which do not respond to radiation or therapy.  Dr. Carla Kim at Children’s Hospital in Boston has 
developed techniques for the isolation of lung cancer stem cells in mice as a powerful model for the 
development of lung cancer in humans. 
Lung
 CancerPrepared September 2010 
2

HOW DO WE PREVENT LUNG CANCER? 

o The primary effort in prevention of lung cancer remains focused on discouraging use of all 
tobacco products.
o ACS has played a highly visible leadership role both in the US and abroad to reduce use of 
tobacco products through education, assistance with cessation, and advocacy for changes in 
state and federal policies.
o Cigarette smoking has declined dramatically since the 1960s falling below 20% in 2007, 
and the ACS continues to support the Society Quitline (1-800-ACS-2345), 24hrs/day, 7days 
per week.
o For more than 30 years, ACS has promoted smoking cessation through the Great American 
Smokeout campaign.
Since almost 90% of lung cancer is associated with smoking, the “easy to understand but hard to do” 
solution is for people to simply not smoke.  Human nature being what it is, there is still much we can 
learn about the most effective delivery of these messages to different segments of the population.  We 
currently fund 5 different projects at a cost >.2M focused on smoking prevention or cessation.  In 
addition, we fund Dr. Jeffrey Petty at Wake Forest University who is doing pioneering work on a 
chemopreventive agent.  
ACS Research Professor Dr. Stephen Hecht at the University of Minnesota is unraveling how tobacco 
related carcinogens are processed by the body.  Dr. Hecht has discovered that each individual is 
genetically and biochemically programmed to process such carcinogens differently which may reveal 
why some smokers never get lung cancer but others do.  In addition, such studies are leading to the 
identification of opportunities for chemoprevention of lung cancer with naturally occurring chemicals 
(e.g. vegetable extracts). 

HOW DO WE DETECT LUNG CANCER? 

o Chest x-rays have shown limited effectiveness as a screening tool for lung cancer. 
o Spiral computed tomography (CT) has shown some promise as a more sensitive screening 
technique. 
o The National Lung Screening Trial was launched in 2002 as a collaboration between the 
National Cancer Institute, the American College of Radiology, and the ACS to determine 
whether screening of high risk individuals for lung cancer will save lives. 
o Novel tests to detect genes, proteins, or tumor cells in sputum are under intense 
investigation in laboratories all over the world. 
Under the umbrella of screening and detection, we fund 11 different projects (>.1M) covering 
biomarker development, optical screening, molecular screening and micro-detection of circulating 
tumor cells.  This is a very exciting area attempting to meet the substantial unmet medical need to 
provide a much more effective approach to the detection of lung cancer. Prepared September 2010 
3
Dr. Dan Kadrmas, a radiologist at the University of Utah and an ACS grantee, is working on a range 
of highly sensitive imaging techniques including CT, PET, and MRI to more accurately detect tumors 
at earlier times in the disease progression. 

HOW DO WE TREAT LUNG CANCER? 

Treatment of lung cancer remains dependent upon a sometimes effective collection of options 
including surgery, radiation, and chemotherapy.  As there remains a critical unmet medical need for 
more effective therapies, we currently fund 28 research projects (>.6M) focused on improvement of 
the therapeutic options for lung cancer. 
o During the past 5 years, monoclonal antibodies and tyrosine kinase inhibitors have had shown 
the greatest activity against lung cancer when used in combinations with traditional 
chemotherapy. 
o Today there are more than 1000 open clinical trials in lung cancer many focused on the 
establishment of optimal drug combinations including the plethora of new targeted therapies.   
The epidermal growth factor receptor (EGFR) is important for the growth of cells and is often over 
expressed in lung cancer.  Iressa is a drug which inhibits EGFR very effectively but only benefits about 
10-15% of patients.  This molecular and clinical puzzle is being solved by Former ACS grantee, Dr.
Daniel Haber and new grantee (Jan 2009) Dr. Jeffery Engleman at Massachusetts General Hospital, 
and colleagues Dr. Udayan Guha at Sloan-Kettering Institute for Cancer Research, and Dr. Deric 
Wheeler at the University of Wisconsin at Madison. 
o A new targeted agent inhibits the EML4-ALK fusion protein found in a proportion of lung 
cancers has shown very promising activity in early clinical evaluation although ALK fusions 
are found in less than 10% of lung cancers. 

HOW DO WE HELP PATIENTS AND FAMILIES WITH LUNG CANCER? 

o The 5 year survival rate for lung cancer for all stages combined is only 15%; however if the 
disease is detected when still localized, the 5 year survival rate is 49%. 
We currently fund 9 different studies (>.1M) to better understand and improve quality of life, 
survivorship, family care, and palliation for patients with lung cancer.   
Dr. Charles Cleeland, an ACS Grantee at MD Anderson Cancer Center at the University of Texas, is 
working to optimize both assessment and management of the various symptoms following surgical 
treatment of lung cancer.  Dr. Karen Lyons at the Oregon Health and Sciences University is focused 
on the stresses and perceptions that a family must face when a patient is treated for lung cancer.