Caspase-1 in cancer and inflammatory diseases: a potential therapeutic target

Area of Science:

• Molecular Biology
• Immunology
• Cell Biology

Background:

• Caspase-1 is a key protease in inflammasome activation and regulates multiple programmed cell death (PCD) pathways.
• Its activity is modulated by epigenetic factors and post-translational modifications, influencing cancer and immune metabolism.
• Caspase-1's context-dependent roles in the tumor microenvironment highlight its significance in various diseases.

Purpose of the Study:

• To systematically review the paradoxical roles of caspase-1 across different biological networks.
• To integrate knowledge on caspase-1's involvement in PCD, epigenetics, tumor microenvironment, and immune metabolism.
• To analyze therapeutic progress and challenges related to caspase-1 inhibitors.

Main Methods:

• Systematic literature review and integration of data on caspase-1.
• Analysis of regulatory and context-dependent networks of caspase-1.
• Evaluation of therapeutic strategies and clinical outcomes of caspase-1 inhibitors.

Main Results:

• Caspase-1 acts as a master regulator of pyroptosis, apoptosis, necroptosis, ferroptosis, and PANoptosis.
• Its activation is context-dependent within the tumor microenvironment and immune system.
• Significant challenges remain in understanding crossover mechanisms and developing effective caspase-1 inhibitors.

Conclusions:

• Caspase-1 has multifaceted roles in cancer, neurodegenerative, and autoimmune diseases, making it a challenging therapeutic target.
• Current understanding of caspase-1 inhibitor efficacy is limited by insufficient knowledge of its complex regulatory networks.
• Innovative treatment strategies are needed to overcome clinical failures and harness caspase-1's therapeutic potential.