Targeting USP7 in sarcomas: opportunities and challenges

Area of Science:

• Oncology
• Molecular Biology
• Cancer Therapeutics

Background:

• Sarcomas are aggressive mesenchymal tumors with limited advanced treatment options.
• The ubiquitin-proteasome system (UPS) is frequently dysregulated in cancer, presenting therapeutic targets.
• Ubiquitin-specific proteases (USPs), particularly USP7, are emerging as critical vulnerabilities in sarcoma.

Purpose of the Study:

• To review the role of USP7 in the growth and progression of specific sarcoma subtypes.
• To summarize preclinical evidence supporting USP7 as a therapeutic target in sarcomas.
• To explore the potential of USP7 inhibitors in overcoming immune evasion in sarcomas.

Main Methods:

• Literature review of current knowledge on USP7 expression, function, and substrates in sarcomas.
• Analysis of preclinical data on the pathobiological role of USP7.
• Discussion of USP7 inhibitors and their potential application in sarcoma treatment.

Main Results:

• USP7 plays a crucial role in the growth and progression of osteosarcoma, synovial sarcoma, Ewing's sarcoma, and Kaposi's sarcoma.
• Preclinical studies demonstrate USP7's potential as a therapeutic target.
• USP7 is implicated in tumor immune evasion, suggesting USP7 inhibitors could enhance antitumor immunity.

Conclusions:

• USP7 is a promising therapeutic target for various sarcoma subtypes.
• USP7 inhibitors offer a potential strategy to reactivate antitumor immunity in "immunological cold" sarcomas.
• Further research is needed to optimize anti-USP7 therapies, overcome resistance, and design combination strategies.