University of Kentucky
Assessing Glycogen Metabolism as a Therapeutic Target in Ewing’s Sarcoma
Grade Level at Time of Presentation
Junior
Major
Biology
Institution
University of Kentucky
KY House District #
5
KY Senate District #
21
Faculty Advisor/ Mentor
Matthew Gentry, PhD
Department
Department of Molecular and Cellular Biochemistry
Abstract
Ewing’s Sarcoma (ES) is the second most common pediatric bone cancer and affects the bone and surrounding soft tissues of adolescents typically between 10 and 15 years old. Roughly half of ES patients develop a metastatic disease due to the cancer’s aggressiveness, and the long-term survival rate of those with metastatic disease is unfavorable at less than 20%. The current treatment options for ES include chemotherapy in addition to surgery and/or irradiation. This standard of care provides some improvement in disease; however, significant progress in effectively treating ES will likely be contingent on the development of novel approaches.
Glycogen is an important energy storage molecule and acts as an energy currency for the body. Glycogen accumulations have been identified in cancers of the breast, kidney, lung, uterus, head and neck, ovary, bladder, colorectal, and pancreatic tumors, yet the significance of these deposits remains largely unknown. One characteristic of ES is the occurrence of large accumulations that have recently been identified as glycogen.
This project’s aim was to explore the ability of pharmacological interventions to target ES-glycogen. The goal of this project was to identify how preventing the synthesis of glycogen by small molecule inhibition will affect ES cancer progression. We utilized two compounds identified by a collaborator called compound A and E that target glycogen production and tested them as potential therapeutics in ES. We assessed glycogen levels and cell viability on ES tumor cells treated with compounds A and E and each compound’s effects on tumor growth and metabolism in an animal model. Our data demonstrated that ES-glycogen is a novel therapeutic target and established the therapeutic potential of compounds A and E in a preclinical setting. Future studies will determine the minimum treatment regimen, assess re-accumulation of ES-glycogen after treatment, and define an optimal therapeutic window.
Assessing Glycogen Metabolism as a Therapeutic Target in Ewing’s Sarcoma
Ewing’s Sarcoma (ES) is the second most common pediatric bone cancer and affects the bone and surrounding soft tissues of adolescents typically between 10 and 15 years old. Roughly half of ES patients develop a metastatic disease due to the cancer’s aggressiveness, and the long-term survival rate of those with metastatic disease is unfavorable at less than 20%. The current treatment options for ES include chemotherapy in addition to surgery and/or irradiation. This standard of care provides some improvement in disease; however, significant progress in effectively treating ES will likely be contingent on the development of novel approaches.
Glycogen is an important energy storage molecule and acts as an energy currency for the body. Glycogen accumulations have been identified in cancers of the breast, kidney, lung, uterus, head and neck, ovary, bladder, colorectal, and pancreatic tumors, yet the significance of these deposits remains largely unknown. One characteristic of ES is the occurrence of large accumulations that have recently been identified as glycogen.
This project’s aim was to explore the ability of pharmacological interventions to target ES-glycogen. The goal of this project was to identify how preventing the synthesis of glycogen by small molecule inhibition will affect ES cancer progression. We utilized two compounds identified by a collaborator called compound A and E that target glycogen production and tested them as potential therapeutics in ES. We assessed glycogen levels and cell viability on ES tumor cells treated with compounds A and E and each compound’s effects on tumor growth and metabolism in an animal model. Our data demonstrated that ES-glycogen is a novel therapeutic target and established the therapeutic potential of compounds A and E in a preclinical setting. Future studies will determine the minimum treatment regimen, assess re-accumulation of ES-glycogen after treatment, and define an optimal therapeutic window.