AUG 03, 2020 2:57 PM PDT

New research on fusion proteins that may help young patients with synovial sarcoma

New research is published by scientists at Dana-Farber Cancer Institute have discovered new information that may help patients with synovial sarcoma, a highly aggressive and rare cancer. The research was published recently in Nature Structural and Molecular Biology.

"We have for the first time defined the molecular basis for the cancer-specific targeting properties of the culprit fusion protein, SS18-SSX, found in 100% of cases of synovial sarcoma," said lead investigator and senior author Cigall Kadoch, PhD. "Importantly, this provides a powerful new therapeutic identification strategy for the drug discovery industry" to synthesize drugs capable of impeding interactions between the abnormal fusion protein and nucleosomes.

Sarcoma is triggered by a cellular anomaly when two proteins are joined to form a fusion protein that then causes malignant malfunctions. When the SS18-SSX fusion oncoprotein replaces the normal SS18 subunit in BAF chromatin remodeling complexes, the wrong chromatin sites are activatedSynovial sarcoma affects muscle tissues in the extremities and mostly affects young people.

In this most recent research, Kadoch and her team expanded upon their past work, identifying the complex process of how the SS18-SSX fusion protein and BAF complexes were targeted to the wrong sites. The process involves the erroneous binding of the fusion protein to the acidic patch on nucleosomes, which ultimately causes the activation of cancer-related genes.

The authors write in their publication, “Our results describe a functional interplay between a key nucleosome binding hub and a histone modification that underlies the disease-specific recruitment of a major chromatin remodeling complex.”

The investigators hope their findings will inform the drug development industry to help produce better treatment options for patients. As Kadoch concludes, "these results suggest that inhibition of the interactions between SS18-SSX-bound BAF complexes and H2AK119Ub -marked nucleosomes using small molecules or peptides may prove a viable therapeutic strategy for synovial sarcoma."

Sources: Nature Structural and Molecular Biology, Eureka Alert

About the Author
  • Kathryn is a curious world-traveller interested in the intersection between nature, culture, history, and people. She has worked for environmental education non-profits and is a Spanish/English interpreter.
You May Also Like
JUL 13, 2020
Cancer
Breast cancer patients are 60% more likely to die of cancer after surviving a heart attack
JUL 13, 2020
Breast cancer patients are 60% more likely to die of cancer after surviving a heart attack
Unwelcome news from researchers at NYU Grossman School of Medicine suggests that breast cancer patients are 60% more lik ...
JUL 14, 2020
Drug Discovery & Development
How Cancer Cells Influence Drug Responses
JUL 14, 2020
How Cancer Cells Influence Drug Responses
When studying a large number of brain samples, researchers were able to characterize how changes in cells influence drug ...
AUG 05, 2020
Cancer
A New Test to Analyze Cell-Free DNA in Cancer Diagnostics
AUG 05, 2020
A New Test to Analyze Cell-Free DNA in Cancer Diagnostics
Cell-free DNA (cfDNA) are small pieces of genomic DNA that have escaped into the bloodstream either through active relea ...
AUG 04, 2020
Cancer
Commonly used pesticides, approved by EPA, linked to mammary gland tumors
AUG 04, 2020
Commonly used pesticides, approved by EPA, linked to mammary gland tumors
In an analysis of how regulators review pesticides for their potential to cause cancer, researchers at Silent Spring Ins ...
AUG 06, 2020
Immunology
Resetting the Body's Danger Sensor
AUG 06, 2020
Resetting the Body's Danger Sensor
The human body has a sophisticated danger-sensing mechanism that alerts the immune system when something is not right. T ...
SEP 16, 2020
Cancer
Does Discontinuation of Immunotherapy Effect Final Results in Metastatic Melanoma?
SEP 16, 2020
Does Discontinuation of Immunotherapy Effect Final Results in Metastatic Melanoma?
The last decade has seen the emergence of several new therapies against cancer. For melanoma, checkpoint inhibitors have ...
Loading Comments...