Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Comparative oncology reveals DNMT3B as a therapeutic vulnerability in soft-tissue sarcoma Undifferentiated pleomorphic sarcoma (UPS), an aggressive subtype of soft-tissue sarcoma (STS), is exceedingly rare in humans and lacks effective, well-tolerated therapies. In contrast, STS are relatively common in canine companion animals; thus, incorporation of veterinary patients into studies of UPS offers an exciting opportunity to develop novel therapeutic strategies for this rare human disease. Genome-wide studies have demonstrated that UPS is characterized by aberrant patterns of DNA methylation. However, the mechanisms and impact of this epigenetic modification on UPS biology and clinical behavior are poorly understood. Leveraging cell lines and tissue specimens derived from human and canine patients, we discovered that the DNA methyltransferase DNMT3B is overexpressed in UPS relative to normal mesenchymal tissues and associated with a poor prognosis. Consistent with these findings, genetic DNMT3B depletion strongly inhibited UPS cell proliferation and tumor progression. However, existing hypomethylating agents, including the clinically approved drug 5-aza-2-deoxycytidine and the DNMT3B-inhibiting tool compound nanaomycin A, were ineffective in UPS due to cellular uptake and toxicity issues. Thus, further development of DNMT3B-targeting strategies for these patients is critical.
3
The categories of this paper are: evolutionary
12
The categories of this paper are: behavior
6
The categories of this paper are: plant
13
The categories of this paper are: animal
31
The categories of this paper are: paleontology
21
The categories of this paper are: toxicology
10
The categories of this paper are: and
5
The categories of this paper are: cell
23
The categories of this paper are: immunology
8
The categories of this paper are: genomics
18
The categories of this paper are: systems
28
The categories of this paper are: communication
29
The categories of this paper are: education
0
The categories of this paper are: genetics
14
The categories of this paper are: biophysics
17
The categories of this paper are: molecular