Highlights in USP7 inhibitors for cancer treatment

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• Ubiquitin-specific protease 7 (USP7) is a deubiquitylating enzyme critical for regulating proteins involved in cancer.
• Abnormal USP7 expression correlates with poor prognosis in various malignancies, highlighting its therapeutic potential.
• Despite its promise, no USP7-targeting drugs have reached clinical trials, necessitating further research.

Purpose of the Study:

• To review the role of USP7 as a drug target in cancer therapy.
• To summarize small molecule USP7 inhibitors, including their scaffolds, activities, and binding modes.
• To discuss challenges in developing USP7 inhibitors and potential combination therapies.

Main Methods:

• Systematic literature review of USP7 inhibitors.
• Analysis of reported scaffolds, biological activities, and binding interactions.
• Discussion of drug development challenges and therapeutic strategies.

Main Results:

• USP7 regulates key proteins in tumor suppression, transcription, epigenetics, DNA repair, and immune response.
• Numerous small molecule inhibitors targeting USP7 have been identified with varying potencies and selectivities.
• Pre-clinical data suggest USP7 inhibitors hold promise for cancer treatment.

Conclusions:

• USP7 is a validated and druggable target for cancer therapy.
• Further research is needed to overcome development challenges for USP7 inhibitors.
• Combination therapies involving USP7 inhibitors may offer new avenues for treating resistant tumors.