Overcoming Resistance to Immunotherapy in Renal Cancer by Targeting Telomerase
Abstract
Tumors exhibit features that differentiate them from normal cells, alert the immune cells, and allow them to be recognized and eliminated under normal conditions. In cancer patients, tumors are able to bypass these mechanisms, suppress the immune system, and outgrow. Recent efforts have resulted in better understanding of particular interactions between tumor cells and immune cells called immune checkpoint pathways. Treatments that block the immune checkpoint pathways and release the break on the immune cells were tested in renal cancer patients. Unlike systemic chemotherapies, immune-modulating treatments caused fewer general toxicities and more durable responses in a subset of patients. Unfortunately, therapeutic responses to immunotherapies were limited to a small subset of renal cancer patients highlighting the urgency to develop other types of immunotherapies. The ends of chromosomes, i.e., telomeres, cannot be replicated as the rest of the chromosomes in the cells and thus get shorter with each cell division, marking a cell s age. Cells are equipped with the proper machinery to detect the short telomeres to stop cell division when these structures become very short. Unlike normal cells, a majority of cancer cells activate an enzyme called telomerase to replicate these parts of the chromosomes to bypass these normal cellular defense mechanisms and become immortal. Telomerase is essential for the survival of cancer cells but not normal healthy cells, making it a viable therapeutic target. We are proposing to utilize a molecule that interferes with the function of telomerase and to stop renal cancer cell growth. Additionally, we propose that this molecule not only can kill cancer cells in a culture dish, it can potentially activate the host immune system against the tumor because of the unique way this molecule targets cancer cells. We propose to test (Aim 1): Whether telomerase targeting induces certain immune responses, and (Aim 2): Whether we can sensitize an immunotherapy-resistant renal cancer model to immunotherapy by targeting telomerase. Thus, we are addressing the developing novel treatments area of emphasis of the Kidney Cancer Research Program.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110856
Entities
People
- Esra A Akbay
Organizations
- United States Army
- University of Texas Southwestern Medical Center