National Cancer Institute


Avasopasem Shields Normal Cells from Radiation, Helps Kill Cancer Cells

What is the aim of Cancer treatments? Cancer treatments aim to kill cancer cells. Other treatments often used to help people with cancer, called supportive therapies, protect normal tissues or make the side effects from cancer treatments more bearable. What if one drug could play both of these roles at the same time? In new studies in mice, researchers found that a drug called avasopasem manganese (AVA), which has been found to protect normal tissues from radiation therapy, can also make cancer cells more vulnerable to radiation treatment. AVA provides this dual effect by exploiting the differences in the way normal and tumour cells produce hydrogen peroxide, explained Douglas Spitz, PhD, professor of radiation oncology at the University of Iowa, who helped lead the study. With any cancer treatment, “you try to find this sweet spot where you’re balanced between an effective therapeutic dose for killing cancer cells, but not causing excessive harm to normal tissues,” said Michael Espey, PhD, of NCI’s Division of Cancer Treatment and Diagnosis, who was not involved in the study. “If you can [have a single drug that] lowers the toxicity in normal tissues while increasing the toxicity in cancer cells, then you really have sort of a game-changer.” More work is needed to see if the effects observed in mice can be replicated in people. But in April, Galera Therapeutics, which manufactures AVA, reported positive findings from a small clinical trial of AVA added to a targeted form of radiation therapy in people with pancreatic cancer. Two other ongoing clinical trials are also testing AVA in combination with radiation therapy in lung and pancreatic cancer. Building on Cells’ Natural Defense Mechanisms In radiation therapy, high doses of x-rays or other charged particles are aimed at a tumour. The radiation can damage cancer cells’ DNA to the point where the cells stop dividing or die. While a single radiation dose is administered in minutes, many of the resulting changes in cells that cause them to die take days to occur. When a dose of radiation hits a cell, its high energy creates compounds called free…

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Study provides genetic insights into osteosarcoma in children

New York 19th March 2020 : A study by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, offers new insight into genetic alterations associated with osteosarcoma, the most common cancerous bone tumour of children and adolescents. The researchers found that more people with osteosarcoma carry harmful, or likely harmful, variants in known cancer-susceptibility genes than people without osteosarcoma. This finding has implications for genetic testing of children with osteosarcoma, as well as their families. The study was published March 19, 2020, in JAMA Oncology. “With this study, we wanted to find out how many people with osteosarcoma may have been at high risk for it because of their genetics,” said Lisa Mirabello, Ph.D., of NCI’s Division of Cancer Epidemiology and Genetics (DCEG), who led the research. “We not only learned that at least a quarter of the people in the study with osteosarcoma had a variant in a gene known to predispose someone to cancer, we also uncovered variants that had never before been associated with this cancer.” In the study, the researchers looked for harmful (or likely harmful) variants in 238 known cancer-susceptibility genes in DNA samples from 1,244 people with osteosarcoma and compared the frequency of such variants with that in people in a cancer-free control group. They identified a harmful or likely harmful variant in a known cancer-susceptibility gene in 28% of the people with osteosarcoma. By contrast, only 12% of people in the cancer-free control group had such a variant. When the authors looked at a subset of 166 genes that are known to be inherited in an autosomal dominant fashion—that is, where inheriting one alteration from one parent is sufficient to increase cancer risk—they saw harmful or likely harmful variants in about 18% of the patients but only 5% of controls. And another 25% of the patients had a rare variant of uncertain significance that was predicted to be harmful. Patients who had harmful variants were younger at age of osteosarcoma diagnosis, on average, than patients who did not (15.3 years versus 16.9 years). In addition, the youngest children…