New discovery in Ewing’s sarcoma could prevent the onset of tumor metastases

A new finding in Ewing’s sarcoma, an aggressive and often fatal childhood cancer, has revealed the potential to prevent cancer cells from spreading beyond their primary tumor site.

This breakthrough provides new insight into what triggers the process that allows cancer cells to survive while traveling through the body in the bloodstream.

Researchers at the University of British Columbia and BC Cancer have learned that Ewing’s sarcoma cells – and possibly other types of cancer cells – are able to develop a shield that protects them from the harsh environment circulation and other places when looking for a new place to settle or metastasize. The study has just been published in Discovery of cancer.

“You might think that a tumor cell could easily survive in the bloodstream, but it’s actually a very difficult environment,” said lead author of the study, Dr. Poul Sorensen, a distinguished scientist at BC Cancer, professor of pathology and medicine at the new Academy of Translational Medicine, Faculty of Medicine, University of British Columbia.

“What we found is that Ewing’s sarcoma cells are able to develop an antioxidant response that protects them and allows them to survive while in circulation,” said Dr Sorensen. “It’s like a person in the Arctic who has to put on a thick layer before going out. If they don’t protect themselves, they are exposed to dangerously harsh conditions in which they may not survive.”

Metastatic disease, which occurs when cancer has spread throughout the body, is the strongest predictor of poor outcome for cancer patients of all ages and has been a difficult process for researchers or clinicians to study. target.

“What’s exciting about this study is that if we can target the circulating cells, we may be able to prevent metastasis from occurring. So this is the main objective of this research, ”said Dr Sorensen.

Few cells can become metastatic. Although there has been research into the genetic reasons for a tumor mutating and spreading, what these researchers found is that Ewing’s sarcoma cells activate the expression of a natural gene to the surface of the cell, known as IL1RAP, to create a protective shield of proteins. .

This study is the first to show that the surface protein, IL1RAP, is rarely expressed in normal tissue, but is upregulated in childhood sarcomas. This is a very good thing because it means that we can develop treatments to target IL1RAP without producing toxic side effects in non-cancerous cells. “

Dr Haifeng Zhang, UBC postdoctoral fellow in Dr Sorensen’s lab at BC Cancer and first author of the study

Drs. Colleagues Sorensen and Zhang, who are members of the St. Baldrick’s Foundation-Stand Up To Cancer Pediatric Dream Team, as well as the National Cancer Institute Pediatric Immunotherapy Discovery and Development Network (PI-DDN), have developed antibodies that can target IL1RAP.

“These powerful antibodies can bind to the outside of the cell, and we show in our research that these reagents can actually kill Ewing’s sarcoma cells. So not only have we discovered an interesting path, but we are well on the way to developing a clinic. A quality immunotherapeutic treatment for Ewing’s sarcoma, ”said Dr Sorensen.

“We are optimistic that we will be able to work on clinical trials in a year or two,” added Dr Zhang.

Research is ongoing to determine if the same protective behavior can be found in other types of cancer cells, including acute myeloid leukemia, melanoma, pancreatic adenocarcinoma, central nervous system tumors, and in certain types. lung and breast cancer.

Source:

Journal reference:

Zhang, HF., et al. (2021) Proteomic screens for anoikis suppressors identify IL1RAP as a promising surface target in Ewing’s sarcoma. Discovery of cancer. doi.org/10.1158/2159-8290.CD-20-1690.


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Hector Hedgepeth

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