Targeting the ubiquitin-proteasome system and drug therapy in colorectal cancer

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Colorectal cancer (CRC) is a major global health concern, ranking as the third most common malignancy and second leading cause of cancer deaths.
• Limited therapeutic options and poor prognosis highlight the urgent need for innovative CRC treatment strategies.
• The ubiquitin-proteasome system (UPS) is crucial for protein homeostasis and significantly impacts CRC initiation, progression, tumor immunity, and chemotherapy resistance.

Purpose of the Study:

• To explore the therapeutic potential of targeting the ubiquitin-proteasome system (UPS) for colorectal cancer (CRC).
• To review emerging strategies that modulate UPS activity for improved CRC treatment outcomes.
• To highlight novel approaches like PROTACs and molecular glues in CRC therapy.

Main Methods:

• Review of current literature on the ubiquitin-proteasome system (UPS) in colorectal cancer (CRC) pathogenesis.
• Analysis of small-molecule compounds and emerging technologies targeting the UPS for CRC treatment.
• Examination of how UPS modulation impacts oncogenic protein degradation and tumor progression.

Main Results:

• Small-molecule inhibitors targeting UPS enzymes (E1, E2, E3) or the proteasome show therapeutic promise in CRC.
• These drugs effectively degrade oncogenic proteins, thereby impeding tumor progression.
• Emerging technologies like proteolysis-targeting chimera (PROTAC) and molecular glues offer new avenues for selective oncogenic protein degradation.

Conclusions:

• Targeting the ubiquitin-proteasome system (UPS) represents a promising strategy for colorectal cancer (CRC) treatment.
• Modulating UPS activity can effectively impede tumor progression by degrading oncogenic proteins.
• Novel therapeutic modalities, including PROTACs and molecular glues, provide new opportunities for enhancing CRC treatment efficacy.