Defining Cellular and Genetic Factors for Renal Cell Carcinoma Subtypes
Abstract
Cancer is one of the most common human genetic diseases. It is caused by genetic changes that lead to dysregulation in cell growth and death. Understanding what these changes are and which genes they occur in is critical for us to fight cancer. Due to recent advancements in biotechnology, we have been able to identify a large number of these cancer-associated genes in patient samples, and with research programs like The Cancer Genome Atlas (TCGA), these genetic changes have been used to subclassify cancers into more well-defined groups for treatment. For example, in general, all kidney cancers have been treated with the same therapies, but this research has given us an understanding that not all kidney cancers are equal. They can be further classified into subgroups based on their genetic changes and appearances and should be treated differently. A deeper understanding of what genetic changes are associated with each kidney cancer subtype will better inform clinicians on how to treat each case. Our research proposal will focus on two FY21 KCRP focus areas: (1) Conducting basic biology research to better understand etiology and cancer progression, metastatic disease, refractory disease and therapeutic resistance, genetic and environmental risk factors, and the prevention of kidney cancer, and (2) Defining the biology of rare kidney cancers and develop treatments to improve outcomes and reduce death. The objective of this research project is to define recurrent genetic alterations that can initiate kidney cancer and determine which normal kidney cell types can turn into cancer cells. Currently, research on this disease has been limited by the availability of clinically relevant animal and cell line models. These models do not encompass the diversity of genetic changes that have been previously observed in research to be associated with kidney cancer; therefore, new preclinical kidney cancer models need to be developed. Using an experimental approach developed by Dr. Park s laboratory, called human cell transformation assay, we can engineer normal human cells into cancer cells by manipulating specific cancer-associated genes. This method allows choosing which genes to change so that each model will better mimic what is seen in patients. Our proposal will create a panel of these kidney cancer cell lines that encompass kidney cancer subtypes that are currently known. These disease models can then be used to screen for new drugs and therapies that can target each specific subtype. Although this is a basic research project, the results from this study can lead to clinically relevant therapies within the next five to ten years. One group of people who are affected by kidney cancer are members of the military. While Veterans and Service Members on active duty serve this country, they are exposed to various cancer risk factors such as chemical exposures and tobacco use. These hazards have been intensively investigated and are established to cause DNA damage to genes that are associated with kidney cancer. These genetic mutations likely contribute to the high incidence of kidney cancer in Veterans in the United States. Unfortunately, as previously addressed, the current treatment for certain subtypes of kidney cancer is limited. Many of our men and women in uniform -- when this cancer as a metastatic form is found -- are considered untreatable. The research proposed in this project will help us to better understand the relationship between the various kidney cancer subtypes and the genes that cause them. It will also provide us with valuable preclinical kidney cancer models that can be used for drug screens. This research will ultimately lead to the development of new therapeutic approaches for subtype-specific precision medicine.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210482
Entities
People
- Jung Wook Park
Organizations
- Duke University
- United States Army