Researchers discovered a gene related to bone cancer in children, a potential new ID therapy

0
36


Researchers have discovered a gene, OTUD7A, that affects the development of Ewing’s sarcoma, a bone cancer that occurs primarily in children. They have also identified a compound that shows potential to block the activity of the OTUD7A protein. The finding, made by scientists at the University of North Carolina and the Lineberger Comprehensive Cancer Center, appeared online on June 1, 2021 at Advanced sciences.

About 250 children and they are diagnosed with Ewing each year in the U.S. About half of those diagnosed will ultimately succumb to the disease, pointing to the need for better therapies.

“Our main research focus was on the EWS-FLI1 fusion protein found in approximately 85 percent of patients with Ewing’s sarcoma,” said Pengda Liu, PhD at UNC Lineberger, Assistant Professor of Biochemistry and Biophysics at the UNC School of Medicine and co-lead author. “This protein, made up of chunks of two other proteins, is unique to Ewing’s sarcoma and only occurs in , which makes it an excellent target for treatment. “

Critical protein relationships contribute to the development of cancers such as Ewing’s sarcoma. Therefore, it was a fundamental discovery when UNC researchers found that OTUD7A controls the -which causes fusion protein.

Armed with this knowledge, scientists went in search of this could block OTUD7A activity. His collaborator, Atomwise Inc., used an artificial intelligence program known as AtomNet to analyze four million small molecules to find one that could fit in an OTUD7A pocket. One compound they identified, 7Ai, showed good ability to reduce tumor formation in mice grafted with human Ewing sarcoma cells. The compound did not appear to be toxic and was well tolerated. In addition, 7Ai did not kill normal cells that were tested in laboratory culture experiments.

“Treatment with 7Ai could provide a new specific therapeutic option for patients who become resistant to chemotherapy. The development of an effective drug will require more lab work and then clinical studies,” Liu said.

“By deeply exploring the key cellular processes that lead to cancer, unexpected therapeutic pathways may prove possible,” said co-author Ian Davis, MD, Ph.D., G. Denman Hammond, childhood cancer professor and co-leader of cancer. Genetics program at UNC Lineberger. “Once the validated our biological approaches, the application of virtual computational screening allowed us to quickly identify a lead molecule to test and validate it ”.

Researchers are currently working with UNC Eshelman School of Pharmacy to improve the potency and specificity of 7Ai.

“I am particularly indebted to a UNC student with Ewing’s metastatic sarcoma who made it a priority to donate tissues that could be used for research,” said Davis, who is also the associate head of hematology division. -pediatric oncology. “We are also grateful for funding our research through a NIH Beau Biden Pediatric Cancer Moonshot Fellowship, which emerged after the death of President Biden’s son related to cancer.”


The discovery of childhood cancer can stop the spread of the tumor before it begins


More information:
Advanced sciences (2021). DOI: 10.1002 / advs.202004846

Citation: Researchers discovered a gene related to bone cancer in children, a new potential identifying therapy (2021, June 1), retrieved June 1, 2021 at https://medicalxpress.com/news/2021-06 -gene-linked-bone-cancer-children. html

This document is subject to copyright. Apart from any fair treatment for the purposes of private study or research, no part may be reproduced without written permission. Content is provided for informational purposes only.





Source link