Currently, there are no approved treatment interventions to mitigate or treat the side effects of radiation cancer treatment, either acutely or chronically. Complications associated with radiation therapy can sometimes impart a toxicity burden on cancer patients that may result in treatment interruptions, hospitalizations, poor prognosis, or reduced quality of life.

The division is addressing this unmet need by expanding on the substantial scientific and financial investment from the U.S. government to move promising therapeutics towards clinical trials to mitigate and/or treat the side effects of radiation therapy.

Toxicities being addressed in preclinical models include (but are not limited to): pneumonitis/lung fibrosis after thoracic radiotherapy for breast cancers, lung cancers, lymphomas, and thymomas, and neurocognitive decline associated with whole brain radiation. With this, the division is making significant strides to reduce the psychological, social, and economic burden imparted on cancer survivors and the healthcare system.

Research Highlights

Radiation Pneumonitis/Fibrosis

• Development of well-characterized small and large models that recapitulate radiation pneumonitis/fibrosis in humans in order to strengthen the predictive value of data generated in the laboratory to improve quality of life outcomes in radiation cancer treatment and increase the likelihood for survival in a radiological or nuclear accident or attack.
• Models take into consideration physical, environmental, and biological parameters to ensure a high degree of reproducibility. Using these well-characterized models, division researchers are focused on understanding the pathophysiological mechanisms of radiation toxicity using classical molecular biology, various “omics” approaches, and disease-progression modeling.
• Seminal work conducted by investigators within the division led to the identification of tissue hypoxia and chronic oxidative stress as major contributing factors facilitating pro-fibrogenic and pro-inflammatory signaling in lung injury after radiation therapy. These data defined a new mechanistic paradigm of radiation-induced lung injury (RILI) and provided the basis for the development of pharmaceutical interventions to mitigate and/or treat RILI.
• Division researchers have moved multiple novel therapeutics screened in preclinical models within the division towards Food and Drug Administration Investigational New Drugs (FDA IND) and Phase I and II clinical trials.
• Endpoints include radiographic and functional changes, quantification of fibrosis using hydroxyproline assay, measurements of edema/congestion, histology.

Gastrointestinal (GI) Toxicity

• Well-characterized models of whole abdominal irradiation in rodents. Endpoints include GI function, nutrient absorption, motility, microbiome, hemorrhage and ulceration, histology.
• Major goal of research within the division is to elucidate the mechanisms of interactions between hematopoietic and nonhematopoietic cells in acute and chronic pathologies of the GI tract. Investigators in the division have focused on the impact of these interactions on GI function in the context of irradiation as well as non-radiation-related diseases, including obesity, host–pathogen interactions, and inflammatory bowel disease.
• Research is also focused on understanding the mechanisms of brain–gut function following whole abdominal irradiation and partial-body irradiation in rodents.

FLASH Radiotherapy

Learn more about department research in FLASH radiotherapy.

Contact

For more information, contact Erika Davies, PhD at erika.davies@som.umaryland.edu.