An Inducible CRISPR Platform for Orthogonal Control of Gene Expression in Lung Cancer Formation
Abstract
Scientific Objective and Rationale: Next-generation sequencing of human lung tumors has identified a large collection of genetic alterations and expression changes. However, determining which of these are important in lung cancer remains a major challenge. Here, we propose a new platform based on the CRISPR/Cas9 system that will allow researchers to rapidly turn on and off several genes at once to test their respective roles in lung cancer formation and determine how they cooperate with each other. This system is toggle-able, so the contribution of each gene or gene combination during different stages of tumor formation and subsequent tumor spread may be studied as well. The utility of this novel platform will help to understand the molecular mechanisms of initiation and progression to clinically significant lung and cancer and to understand the contributors to lung cancer development other than tobacco. Applicability: Lung cancer is the leading cause of cancer-related death for both men and women in the United States and accounts for 20% of cancer diagnoses among the U.S. Veteran patient population. Approximately 40% of all non-small cell lung cancers (NSCLCs) have no clear known driver mutations, so a platform such as this can aid in the identification and confirmation of new genetic determinants of lung cancer. This system can also be used in high-throughput, in vivo drug screens to find new therapies for lung cancer. This is the first step in matching genetic alterations with potential therapy. If druggable targets are identified (likely amplifications or gene overexpression using this platform) and Food and Drug Administration-approved drugs exist, clinical applications may be relatively short—within 3-5 years. Furthermore, by understanding the molecular mechanisms of lung cancer progression, one can identify new biomarkers and therapies that would aid in the diagnosis, prognosis, and treatment of lung cancer patients globally across all stages.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810551
Entities
People
- Victoria Wang
Organizations
- United States Army
- University of California, San Francisco