December 4, 2009

Discovery Lecturer outlines lung cancer’s progression

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MIT’s Tyler Jacks, Ph.D., discusses his team’s cancer research during his recent Discovery Lecture. (photo by Susan Urmy)

Discovery Lecturer outlines lung cancer’s progression

Tyler Jacks, Ph.D., and his colleagues have enlisted an army of mice in their quest to understand the genetic events that contribute to cancer development.

By making multiple genetic mutations that predispose the mice to cancer, the group has been able to study the process of cancer growth as it unfolds.

In his recent Discovery Lecture, Jacks, director of the David H. Koch Institute for Integrative Cancer Research at MIT, detailed his team's studies of lung cancer progression.

Lung cancer, he reminded the audience, is the leading cause of cancer

“The survival statistics haven't changed much in the last 50 years, despite advances in treatment,” Jacks said. One of the problems, he noted, is that lung cancer is usually diagnosed at a very late stage, after it has already invaded local tissue or moved to distant sites in the body.

“We need to understand the details of disease progression so we can discover new tools, new agents to treat the disease, or to prevent its emergence, or to detect it at earlier and earlier stages.”

Jacks and his colleagues have focused on non-small cell lung cancer, which accounts for about 80 percent of lung cancers. Two genes — k-ras and p53 — top the list of genetic contributors to non-small cell lung cancer, and Jacks' group has developed mouse models with mutations in these two genes.

The mice develop lung tumors that start as an overgrowth of cells (hyperplasia) and progress to contained, non-invasive tumors and then to advanced stage adenocarcinomas that metastasize to distant organs. Using these models, the investigators are systematically studying lung cancer progression and discovering signaling pathways that participate in each of the steps along the way.

They have found that genetic “signatures” that distinguish metastatic tumors from non-metastatic tumors in the mouse can be used to classify early human lung cancers as well.

Jacks is an investigator of the Howard Hughes Medical Institute (HHMI) and a member of the National Academy of Sciences and the Institute of Medicine.

For a complete schedule of the Discovery Lecture series and archived video of previous lectures, go to