Genetically Informed Approaches to Lung Cancer's Complexity - National Cancer Institute

An estimated 220,000 individuals were diagnosed with some form of lung cancer in 2010. It is the leading cause of cancer-related death, with more than 157,000 predicted deaths in 2010. 

Smoking is far and away the most important risk factor for lung cancer. It is evident that risk increases with the number of cigarettes smoked per day and the duration of smoking. Deaths from lung cancer have been decreasing in men since 1990, but have been stable in women since 2003 after continuously rising for several decades. These trends reflect historical differences in smoking between men and women, and the decrease in smoking rates over the past 40 years.

The cancer community is poised to take advantage of the convergence of genetic information, appropriate screening techniques, and new targeted therapies for lung cancer. For the enormous number of individuals who will face a diagnosis of lung cancer this year, any brighter outlook is most welcome.

 

 

I think it’s an exciting time now, because if we can influence early diagnosis and prevention of lung cancer, and care of discovered lung cancer, we could actually make a major change to total cancer mortality in the United States. [Already] the total cancer mortality has gone down over the past five to ten years mainly due to decreases in cigarette smoking.
-John Minna M.D.
University of Texas Southwestern Medical Center

 

Lung Cancer is Not a Single Disease

 

When we say lung cancer, we are actually referring to four different subtypes. Three subtypes are non-small cell lung carcinomas, or NSCLC: adenocarcinoma, squamous cell carcinoma, and large cell carcinoma; the fourth subtype is small cell carcinoma. This first-level classification is likely to be the start of solving a complicated challenge of linking diagnostic characteristics to the most effective treatments.

NCI-supported researchers are beginning to uncover genetic drivers of these four subtypes and applying this molecular knowledge for clinical benefit. However, it is clear that the best in diagnostic technologies and therapeutic advances will be needed to make significant progress in treating this very complex collection of diseases. Ideally, this will be complemented by down-ward trends in smoking rates, which is the most effective way to reduce the burden of lung cancer.

 

Crizotinib: A Promising New Targeted Drug

 

There are currently several mutations that are known to exist in lung cancer, including EGFR and RAS gene mutations in non-small cell lung cancer. As with melanoma and some other cancers, BRAF gene mutations have also been found in lung cancers.

In 2007, researchers identified a genetic target known as a gene translocation, or movement of a gene fragment from one chromosomal location to another. The translocated gene, EML4-ALK—found in 5 percent of NSCLC patients—can be acted on by crizotinib, a promising new drug with minimal side effects.

Crizotinib acts by blocking the ALK kinase, believed to promote tumor growth. Results from this phase I trial showed that more than half of treated patients experienced tumor shrinkage while 33 percent had their tumors stabilize.

The development of crizotinib was made possible through molecular tumor characterization that was conducted at NCI-designated Cancer Centers. The drug was first tested against anaplastic large-cell lymphoma as well as on neuroblastoma and NSCLC cells grown in the laboratory. Preliminary results of the phase I trial were so promising that a trial testing crizotinib in children with neuroblastoma was launched less than six months after the release of the results.

While efforts to further decrease smoking rates are critical, there is also great opportunity to utilize molecular and genetic information to significantly improve the treatment options available to patients diagnosed with lung cancer. This will require continued investigation into the biology of the various types of lung cancer and coordination between laboratory and clinical researchers to optimize existing treatment strategies and develop new ones. Crizotinib received FDA approval in 2011.

(From Cancer | Changing the Conversation: The Nation's Investment in Cancer Research – 2012)

Genetically Informed Approaches to Lung Cancer's Complexity - National Cancer Institute