A Human Pluripotent Stem Cell-Based Approach to Identifying the Drivers of Pulmonary Carcinoid
Abstract
One of the rare types of lung cancer, called pulmonary carcinoid, is composed of the cells with properties of pulmonary neuroendocrine cells (PNECs). There is no big improvement in treatment and prognosis of this cancer during the last 4 decades, and this reflects our limitation in understanding the disease mechanism. The research progress has been hindered by several barriers: (i) Due to a low frequency of pulmonary carcinoid, it is difficult to obtain clinical tumor tissues for in-depth research. (ii) Few cancer cell lines or disease models have been established for robust and reliable mechanistic studies. As a result, no definitive molecular markers or genetic drivers have been identified and little is known on its targets of therapy. Thanks to increasing information about the development of human lung organ, 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. Now we are able to produce the PNEC cells in abundant amounts from human pluripotent stem cells (hPSCs), and convert the normal PNEC into pulmonary neuroendocrine tumors, such as small cell lung cancer. Using the similar strategy of subjecting the PNECs with the genetic factors that are commonly found in pulmonary carcinoid, we expect the cells will undergo transformation into cancer cells and form lung carcinoid-like tumors in mice. The cancerous cells and tumor model will be then characterized on the features of pulmonary carcinoid at morphological and genetic levels. In this project, we will use the novel hPSC-derived PNEC model to effectively and efficiently test the role of the recurrent genetic mutations in causing the tumor initiation and progression. If successful, our study is expected to provide fundamental knowledge about pulmonary carcinoid and facilitate the identification of new prognosis markers or therapy targets.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310636
Entities
People
- Huanhuan Chen
Organizations
- United States Army
- University of Chicago