Using hESC-Derived Lung Cells to Study the Initiation of Small Cell Lung Cancer
Abstract
The lung is the organ in which the largest number of lethal cancer arises in the United States and in the world. Several types of lung cancer are known; each has a characteristic set of behaviors, and each has revealed a certain group of mutations that drive the cancerous behavior. Furthermore, all types of lung cancer occur much more frequently in people who have used tobacco products for many years. One of the most common types of lung cancer, called small cell lung cancer (SCLC), is composed of small cells that have properties similar to normal but relatively uncommon cells in the lung called pulmonary neuroendocrine cells (PNECs). This is a particularly difficult kind of cancer because it is rarely detected before it has metastasized; hence, surgical removal is not possible, and the mortality rate is very high, especially since there are no validated targeted therapies, chemotherapy works only transiently, and immunotherapy has not been successful. Moreover, virtually all patients with SCLC have a strong history of smoking tobacco, so the incidence is higher than average in military personnel. One way to better understand the nature of SCLC and other forms of lung cancer is to define more precisely which cell type in the lung experiences and responds to the mutations commonly associated with the disease. In general, the initiation of most kinds of human cancer is not understood in that way. However, it is now possible to study the first steps in cancer formation with much greater precision, thanks to increasing information about the development of human organs, the availability of methods for differentiating human stem cells in a controlled fashion, new means for isolating thousands of single cells, tools for analyzing their genes and gene expression patterns rigorously, and cell engineering and gene editing methods for making cancer-causing mutations in living cells. We propose to use these new methods and knowledge to try to understand the first steps in the production of SCLC, with a view to reducing the frequency of the disease, advancing the time at which it is diagnosed, and improving therapy by better understanding how it arises and progresses. That means making human PNEC cells in tissue culture from embryonic stem cells, then characterizing the cells before and after being subjected to mutations frequently found in human SCLC. A successful modeling of this process is likely to be useful in studying many other kinds of human cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710223
Entities
People
- Harold E. Varmus
Organizations
- United States Army
- Weill Cornell Medicine