CHAPEL HILL, NC - In a collaborative paper published by Cell Press in the June issue of the journal Cancer Cell, scientists at UNC Lineberger Comprehensive Cancer Center have helped identify proteins responsible for the progression and spread of non-small-cell lung cancer.
The research team, which included UNC Lineberger members Ned Sharpless, MD, D. Neil Hayes, MD, and William Kim, MD, collaborated with researchers at Dana-Farber Cancer Institute and other centers to conduct a comprehensive analysis of gene and protein signals in primary and metastatic lung tumors.
The present works extends observations from a prior 2007 Nature paper from Hayes, Sharpless and collaborators which showed that loss of a tumor-suppressor gene called Lkb1 results in the metastatic spread of lung tumors in mice. In the present work, the group has further defined how inactivation of Lkb1 encourages metastatic spread of cancers. In both human and mouse cells, lack of a working copy of Lkb1 resulted in an increase in activity of proteins that encourage cancer cells to spread throughout the body and form tumors in distant tissues. When these proteins were blocked with targeted pharmaceuticals, there was less tumor metastasis.
“Lung cancer is still the leading cause of cancer deaths worldwide. When these tumors metastasize they can be very difficult to treat,” said Hayes.
“As doctors, we find it very difficult to tell patients when their tumors have spread,” said Kim. “These experiences drive us to do this kind of research, which can help accelerate the development of targeted therapies.”
Sharpless, who is also Associate Director of Translational Research at UNC Lineberger, agrees. “Since drugs have already been identified that target some of the pathways involved, we hope for a more rapid movement of new therapies from the lab to the clinic.”
UNC’s work was carried out using a methodology called “gene expression profiling”, in which scientists get a very powerful look at a given tumor and can precisely determine what genes are “on” and what genes are “off”. Cancers are typically caused by some genes being inappropriately on, and other genes being inappropriately off, thus being able to look at all genes at once and determine which are on is critical to a better understanding of tumor biology.