Novel Organoid Models of Primary Lung Cancer in Decellularized Lung Tissue
Abstract
Lung cancer is the leading cause of cancer-related death worldwide. For most patients, there are limited options for effective treatments, and overall survival at 5 years after diagnosis is 15%. Drug development has been hindered in part due to the lack of availability of good lung cancer models that can be quickly used in an economical fashion. The most widely used inexpensive models consist of lung cancer cells grown in plastic dishes in a manner that is very different from how the cells grow in patients’ lungs. Many of these models no longer grow as they once did in patients and, accordingly, have different drug responses than actual patient tumors. In this project, we propose to develop new methods to improve growth of lung cancer cells outside the patient setting, such that the cancer cells better retain their true biological properties. To accomplish this goal, we will experiment with using mouse lungs as scaffolds in which human lung cancer cells will be grown. Lungs will be harvested from mice and their native cells removed in such a way as to leave behind an intact and functional lung scaffold. Cancer cells from freshly removed fragments of human lung tumors will then be seeded into these scaffolds, chopped into pieces, and grown in Petri dishes in different experimental nutrient broths. Once established, the models will be compared to the matched patient tumor cells from which they were derived to validate their retention of key biological and genetic features. The methods developed in this project to create new and patient-relevant lung cancer models will immediately be applicable to drug discovery research. Accordingly, the project addresses the Lung Cancer Research Program Area of Emphasis of “Identify innovative strategies for prevention and treatment of lung cancer.” We propose to use human lung cancer tissue from the two major forms of lung cancer, adenocarcinoma and squamous cell carcinoma; therefore, we expect our methods to help discover novel treatment strategies for both forms of the disease. Ideally, we aim to develop methods that can be used to grow cells from small tissue fragments so that models can be generated shortly after a patient has undergone a surgical resection or biopsy. In this manner, drug testing can be conducted while the patient is still alive, with the results potentially being used to guide treatment. Since we will be using human patient samples for developing these methods, we expect the methods to immediately have clinical applicability. When considering time to complete the project and publish our findings, we optimistically expect to begin to have a clinical impact within 2-3 years. Overall, the major contribution of this project to the field of lung cancer research will be to address the urgent need for better inexpensive, yet clinically relevant models for drug discovery. Finally, lung cancer is the second most common form of lung cancer among Veterans, with squamous cell carcinoma and adenocarcinoma being the two most common types. Since these types of lung cancer will be the focus of our project, this work is highly relevant to the health of military Service members and Veterans.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910648
Entities
People
- Ming Tsao
Organizations
- United States Army
- University Health Network