黑料吃瓜资源

Scientists at 黑料吃瓜资源 (CSHL) have discovered a new drug target for Ewing sarcoma, a rare kind of cancer usually diagnosed in children and young adults. Their experiments show that the cells causing this cancer can essentially be reprogrammed with the flick of a genetic switch.

Shutting down a single protein forces the cancer cells to take on a new identity and behave like normal connective tissue cells, a dramatic change that reins in their growth. This discovery suggests researchers may be able to stop Ewing sarcoma by developing a drug that blocks the protein known as ETV6.

Ewing sarcoma causes tumors to grow in bones or the soft tissues surrounding them. Once a tumor begins to spread to other parts of the body, it can be very difficult to halt the disease鈥檚 progression. Even for patients with positive outcomes, treating Ewing sarcoma often causes toxic side effects. New treatments are badly needed, says CSHL Professor Christopher Vakoc, who led the research on ETV6.

Vakoc and his colleagues became excited about ETV6 when their experiments revealed that Ewing sarcoma cells seem uniquely dependent on this protein. 鈥淭his protein is present in all cells. But when you perturb the protein, most normal cells don鈥檛 care,鈥� he says. Vakoc notes:

鈥淭he process by which the sarcoma forms turns this ETV6 molecule鈥攖his relatively innocuous, harmless protein that isn鈥檛 doing very much鈥攊nto something that鈥檚 now controlling a life-death decision of the tumor cell.鈥�

Postdoctoral researcher Yuan Gao works in Vakoc鈥檚 lab. When Gao blocked ETV6 in Ewing sarcoma cells grown in the lab, she witnessed a dramatic transformation. 鈥淭he sarcoma cell reverts back into being a normal cell again,鈥� she says. 鈥淭he shape of the cell changes. The behavior of the cells changes. A lot of the cells will arrest their growth. It鈥檚 really an explosive effect.鈥�

Vakoc and Gao hope other researchers will use what they鈥檝e learned to begin exploring potential therapies for Ewing sarcoma that work by switching off ETV6. They say their biochemical analyses, which identify specific spots in the ETV6 protein that are key to its function in cancer cells, could help guide drug development. Because their experiments have shown that most cells are unaffected by the loss of ETV6 activity, they are optimistic that such a drug might be able to eliminate cancer cells while causing few, if any, side effects.

Written by: Jennifer Michalowski, Science Writer | [email protected] | 516-367-8455

Funding

National Cancer Institute, Pershing Square Sohn Cancer Research Alliance, National Institutes of Health, Friends of T.J. Foundation, Christina Renna Foundation, Michelle Paternoster Foundation, William J Riley Foundation, Howard Hughes Medical Institute, The Mary Ruchalski Foundation

Citation

Gao, Y., et al., 鈥淓TV6 dependency in Ewing sarcoma by antagonism of EWS-FLI1-mediated enhancer activation鈥�, Nature Cell Biology, January 19, 2023. DOI: