BUFFALO, NY – February 14, 2025 – A new #review was #published in Oncotarget, Volume 16, on February 12, 2025, titled “SETDB1 amplification in osteosarcomas: Insights from its role in healthy tissues and other cancer types.”

Authors Elodie Verdier, Nathalie Gaspar, Maria Eugenia Marques Da Costa, and Antonin Marchais from the Gustave Roussy Cancer Campus analyzed recent studies on a gene called SETDB1, which may play a key role in osteosarcoma, a type of bone cancer that mostly affects teenagers and young adults. Their review highlights how SETDB1 helps cancer cells grow, resist treatment, and avoid the immune system. Because of this, blocking SETDB1 could be a promising new way to treat osteosarcoma.

Osteosarcoma is a fast-growing bone cancer that is usually treated with surgery and chemotherapy. However, if the cancer spreads or returns, treatment options are very limited. Scientists are searching for new ways to stop this disease, and recent studies have found that osteosarcoma cells often have extra copies of the SETDB1 gene. This seems to make the cancer more aggressive and harder to treat.

“Whole exome sequencing of osteosarcoma samples from both diagnosis and relapses has highlighted several factors, including SETDB1, that are amplified in the most aggressive forms of the disease.”

SETDB1 is involved in epigenetics, meaning it affects how genes are turned on and off without changing the DNA itself. The review explains that SETDB1 helps tumors hide from the immune system, making it difficult for the body to fight the cancer naturally. The researchers believe that blocking SETDB1 could help the immune system recognize and attack osteosarcoma cells. Some experimental drugs that target SETDB1 are already being tested in the lab.

The review also describes how SETDB1 influences key cancer pathways, such as Wnt signaling, which helps cancer cells grow, and epithelial-mesenchymal transition (EMT), a process that allows cancer to spread. The authors suggest that combining SETDB1-blocking drugs with immunotherapy or radiation could be an effective new strategy for treating osteosarcoma.

Another key finding is that SETDB1 may help cancer cells become resistant to chemotherapy, making treatment less effective. This means that drugs targeting SETDB1 could not only slow cancer growth but also make existing treatments work better.

While more research is needed, this review brings attention to SETDB1 as a potential treatment target. Scientists hope that a deeper understanding of SETDB1 will lead to new therapies that improve survival rates for osteosarcoma patients.

DOI - https://doi.org/10.18632/oncotarget.28688

Correspondence to - Antonin Marchais - antonin.marchais@gustaveroussy.fr, and Maria Eugenia Marques Da Costa - jenny.marquescosta@gustaveroussy.fr

Video short - https://www.youtube.com/watch?v=f9WgaDoEubs

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SETDB1 Amplification Identified as a Potential Target for New Osteosarcoma Treatment

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SETDB1 Amplification Identified as a Potential Target for New Osteosarcoma Treatment

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