Modeling the Impact of Radiation Protectors on Radiation-Induced Sarcoma Risk
Abstract
The Fiscal Year 2017 (FY17) Peer Reviewed Cancer Research Program Topic Area focus of this proposal is Cancers in Children, Adolescents and Young Adults, because sarcomas are among the most common cancers arising in children and young adults. The FY17 Military Relevance Focus Area addressed by this proposal is Ionizing Radiation, because Service members may be exposed to radiation, which is a primary risk factor for developing sarcomas. Sarcomas are aggressive tumors that develop from aberrant cells in the muscle, bone, fat, or other connective tissues. Sarcomas subtypes comprise 15% of childhood cancers, and they occur in young adults and adults. Because sarcomas affect children, the impact of years of life lost for sarcoma patients is staggering. The National Cancer Institute estimates that the average years of life lost per person dying of sarcoma is 70.5 years, while for the most common cancers, lung and colorectal, it is 15.1 and 14.0 years, respectively. Exposure to radiation is a primary risk factor for developing a sarcoma. Radiation exposures occur due to nuclear disasters such as the meltdown of Fukashima Diiachi power plant in Japan in 2011 or in the case of a radiological attack from a dirty bomb or nuclear bomb. In these scenarios, primary victims, first responders, and medical workers are at risk of exposure to radiation. Radiation therapy, used to treat half of all cancer patients, is also a significant source of ionizing radiation exposure and with increasing cancer survivorship, the incidence of therapy-related sarcomas is rising. Human exposure to radiation causes life-threatening acute and delayed toxicities. Currently, drug development studies are focused on identifying effective mitigators of the acute radiation syndrome or prophylactic therapies to reduce side effects for cancer patients receiving radiotherapy. The goal is to develop pharmaceuticals to reduce lethal radiation-induced acute toxicity of susceptible tissues. Moreover, radiation and blast trauma can cause injuries to the bone, muscle, and skin that develop into life-threatening sarcomas years later. Major strategies to prevent or mitigate early effects of radiation include drugs designed to block cell death pathways to preserve tissue integrity in radiation-sensitive organ systems. This rational approach to increasing survival from acute radiation syndrome may directly modulate the risk of developing late effects of radiation, specifically sarcomas. Of particular concern, drugs that block the death of cells that have sustained significant radiation damage may increase the development of tumors. We will explore a possible connection between late effects and mitigation strategies that improve cell survival from radiation. These studies are designed to evaluate the long-term effects of preserving cells from irradiated tissues by mitigating acute toxicities. If our hypothesis is correct, these studies will shift the focus of radiation protection and mitigation drug development studies toward regenerative therapies and away from cell death inhibitors to reduce radiation-induced cancer development. Our studies will also examine mechanisms that regulate the development of cancer for individuals exposed to radiation. Our proposal is designed to address multiple long-standing questions in sarcoma biology and emerging concerns about mitigation of acute radiation injury. The conclusions reached from the experiments in this proposal are likely to impact preventative measures for sarcoma development, preventative measures for acute radiation syndrome, mitigation strategies for acute radiation syndrome, cancer screening for individuals exposed to ionizing radiation, radiotherapy planning for cancer patients, and potentially the impact treatment of sarcomas.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810162
Entities
People
- David Kirsch
Organizations
- Duke University
- United States Army