News | Radiation Therapy | May 21, 2021

Experimental Drug Makes Radiation Therapy More Effective, Less Damaging

The experimental drug avasopasem manganese protects healthy tissue while enhancing radiation's capacity to kill cancerous tumor cells by converting superoxide to hydrogen peroxide. Image courtesy of Michael Story, Ph.D.

The experimental drug avasopasem manganese protects healthy tissue while enhancing radiation's capacity to kill cancerous tumor cells by converting superoxide to hydrogen peroxide. Image courtesy of Michael Story, Ph.D.

May 21, 2021 — An experimental drug that has shown promise in protecting healthy tissue from collateral damage caused by radiation therapy for cancer also appears to enhance radiation's capacity to kill tumors, a new study led by UT Southwestern scientists shows. The findings, published online in Science Translational Medicine, could provide a much-needed boost to the radiation treatments used against a variety of tumor types.

The drug, avasopasem manganese (AVA), has already shown promise in clinical trials to prevent a side effect known as acute mucositis. This condition commonly occurs in head and neck cancer patients when radiation therapy damages mucous membranes. However, for this drug to become part of clinical care, it should protect healthy cells from radiation but not cancer cells, explains study leader Michael Story, Ph.D., professor of radiation oncology at UTSW and a member of the Harold C. Simmons Comprehensive Cancer Center.

To determine whether AVA was accomplishing this goal, Story and colleagues at UTSW and the University of Iowa treated cancerous cell lines with this compound before exposing them to radiation. The cancerous cells that received the drug were not protected from radiation and, surprisingly, appeared in some cases to respond more to radiation compared with those that did not receive AVA, particularly at high radiation doses.

This phenomenon also occurred in cancerous cell lines that had been implanted in mice and allowed to grow into tumors. The tumors shrank significantly more when animals were treated with AVA just before receiving a single high dose of radiation, similar to a technique referred to as stereotactic ablative radiotherapy (SAbR), which is used for cancer therapy, compared with those that did not receive the drug. When the treated mice received the drug both before radiation and in the days after, in some cases their tumors disappeared completely.

These positive results in animals were found in several different tumor types, including lung, pancreatic, and head and neck. Further experiments showed that AVA appears to exert its enhanced tumor-killing effects by converting superoxide, which are damaging oxygen ions generated by high doses of radiation, to hydrogen peroxide at levels that overwhelm a tumor's ability to tolerate hydrogen peroxide. Furthermore, using an engineered cell line that overexpressed an enzyme that rids tumors of excess hydrogen peroxide, the anti-tumor effect was nearly eliminated.

Story, a member of the Simmons Cancer Center's Experimental Therapeutics Research Program, notes that AVA is currently being tested in phase 1 and phase 2 clinical trials to enhance therapy, including one clinical trial that combined SAbR with AVA that nearly doubled overall survival in pancreatic cancer patients. "With this drug," he says, "the radiation doses we deliver could be profoundly more effective, while at the same time contribute to protecting adjacent normal tissues."

For more information: www.swmed.edu

Related Content

According to a new study, by the Harvey L. Neiman Health Policy Institute and the American College of Radiology’s National Mammography Database Committee, the most influential radiologist characteristics impacting mammography interpretive performance were geography, breast sub-specialization, performance of diagnostic mammography, and performance of diagnostic ultrasound.

Getty Images

News | Breast Imaging | June 23, 2021
June 23, 2021 — According to a new ...
Master Supply Agreement encompasses clinical development and commercial supply for Clarity’s Cu-67-based candidates to treat neuroblastoma, breast and prostate cancers, among others
News | Radiopharmaceuticals and Tracers | June 22, 2021
June 22, 2021 — NorthStar Medical Radioisotopes, LLC, a global innovator in the development, production and commercia
A phase III clinical trial has validated the effectiveness of the prostate-specific membrane antigen (PSMA)-targeted radiotracer 18F-DCFPyL in detecting and localizing recurrent prostate cancer.

Figure 1. Case example: A 54-year-old man with a history of RP+LND and a subsequent PSA of 1.25 ng/mL had no evidence of disease by baseline imaging. Piflufolastat F 18 (18F-DCFPyL)- PET/CT accurately detected biochemically recurrent prostate cancer with the PSMA PET/CT scan identifying positive left (left panel) and right peri-rectal lymph nodes (right panel).

News | Prostate Cancer | June 21, 2021
June 21, 2021 — A phase III clinica...
Elekta Harmony linear accelerator cleared by U.S. Food and Drug Administration
News | Linear Accelerators | June 18, 2021
June 18, 2021 — Elekta announced that its Elekta Harmony...
SNMMI's Image of the Year is a detailed depiction of areas of cognitive impairment, neurological symptoms and comparison of impairment over a six-month time frame

Figure 1. A: COVID-19-related spatial covariance pattern of cerebral glucose metabolism overlaid onto an MRI template. Voxels with negative region weights are color-coded in cool colors, and regions with positive region weights in hot colors. B: Association between the expression of COVID-19-related covariance pattern and the Montreal Cognitive Assessment (MoCA) score adjusted for years of education. Each dot represents individual patient. C: Results of a statistical parametric mapping analysis. Upper row illustrates regions that show significant increases of normalized FDG uptake in COVID-19 patients at 6-months follow-up compared to the subacute stage (paired t test, p < 0.01, false discovery rate-corrected). Bottom row depicts regions that still show significant decreases of normalized FDG uptake in COVID-19 patients at 6-months follow-up compared to the age-matched control cohort at an exploratory statistical threshold (two-sample t test, p < 0.005). Image Credit: G Blazhenets et al., Department of Nuclear Medicine, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg

News | PET Imaging | June 16, 2021
June 16, 2021 — The effects of COVID-19 on the b
The impact of deploying artificial intelligence (AI) for radiation cancer therapy in a real-world clinical setting has been tested by Princess Margaret researchers in a unique study involving physicians and their patients.

Getty Images

News | Artificial Intelligence | June 15, 2021
June 15, 2021 — The impact of deploying ...
The prevalence of genetic mutations associated with breast cancer in Black and white women is the same, according to a new JAMA Oncology study of nearly 30,000 patients led by researchers in the Basser Center for BRCA at the Abramson Cancer Center.

Getty Images

News | Women's Health | June 15, 2021
June 15, 2021 — The prevalence of genetic mutations associated with breast cancer in Black and white women is the sam
Rensselaer algorithm can identify risk of cardiovascular disease using lung cancer scan #CT
News | Computed Tomography (CT) | June 14, 2021
June 14, 2021 — Heart disease and cancer are the ...
Accuray Incorporated announced the company has received CE Mark certification for its ClearRT helical fan-beam kVCT imaging capability.
News | Radiation Therapy | June 11, 2021
June 11, 2021 — Accuray Incorporated announced the company has received CE Mark certification for its...
The new X-ray scanner can provide detailed information about the internal makeup of rocks, which could be useful for archaeologists studying fossils or miners making decisions about which ore to use in their extraction facilities. Image courtesy of Joel Greenberg, Duke University

The new X-ray scanner can provide detailed information about the internal makeup of rocks, which could be useful for archaeologists studying fossils or miners making decisions about which ore to use in their extraction facilities. Image courtesy of Joel Greenberg, Duke University

News | X-Ray | June 10, 2021
June 10, 2021 — Engineers at Duke University have demonstrated a prot