Race-Related Differential RNA Splicing: Novel Targets for Precision Oncology in Non-Small Cell Lung Cancer
Abstract
African Americans suffer disproportionately from lung and bronchus cancer. They have the highest number of new cases and deaths per 100,000 persons for lung and bronchus cancer. In addition, diagnosis of lung cancer occurs 3 years earlier on average among African Americans compared with whites. Evidence suggests that cigarette smoking patterns and rates are not a primary cause of this disparity. Therefore, there is an urgent need to conduct research to investigate the contribution of other factors to the disparity. These other factors include biological characteristics of the cancer itself. Most of the studies that physicians have done to test treatments for lung cancer have involved a disproportionate majority of white patients. Similarly, most of the studies that scientists have done to identify biological characteristics that cause lung cancer to grow and spread more quickly have used lung cancer samples from a disproportionate majority of white patients. These studies have discovered a limited number of biological characteristics that cause lung cancer to grow and spread more quickly. In addition, there are a limited number of drugs against lung cancer with such characteristics. Thus, there is an urgent need to identify additional, new biological characteristics of lung cancer in African American patients that cause lung cancer to grow and spread more quickly. In addition, there is also an urgent need to do this for military Service members and Veterans, as one of the three most frequently diagnosed cancers among Veterans is lung/bronchus and the military population is racially diverse. Identifying these characteristics will enable us to develop new ways to detect and treat more effectively lung cancer that grows and spreads more quickly in these populations that suffer disproportionately from lung cancer. We have identified a new biological characteristic in lung cancer in African American patients. During normal growth and development, cells in our body use a limited number of genes to make many proteins through an orderly process called splicing. The proteins enable cells in our body to perform all of their normal necessary functions. If this orderly splicing process breaks down then our cells produce proteins not normally made. These proteins can cause cells to grow out of control and spread, causing cancer. We have identified differences in splicing in lung cancer in African American patients. These differences in splicing in lung cancer in African American patients have the potential to cause lung cancer to grow and spread more quickly and influence how lung cancer responds to certain drugs. The work proposed in this application will focus on determining how the splicing differences affect lung cancer cells and whether they do in fact cause lung cancer cells to grow and spread more quickly. In addition, the work proposed in this application will examine how common these splicing differences are in a larger number of lung cancer samples from African American and white patients. Furthermore, the work proposed in this application will assess the relationship between these splicing differences and smoking and lung cancer patient survival. In the proposed work, we will use lung cancer cells in the laboratory established from lung cancer in African American and white patients. We will also use lung cancer samples collected from African American and white patients. Successful completion of this work will be a first step toward developing, within the next 4-8 years, new drugs for lung cancer that grows and spreads more quickly. In addition, this work will be a first step toward developing, within the next 4-8 years, tools to detect lung cancer that grows and spreads more quickly and predict whether lung cancer is likely to be stopped by particular drugs. Therefore, the research described in this proposal will address two LCRP Areas of Emphasis, identifying innovative strategies for the tr
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010483
Entities
People
- Jennifer Freedman
Organizations
- Duke University
- United States Army