Targeting proliferating cell nuclear antigen (PCNA) for cancer therapy

Area of Science:

• Molecular Biology
• Cell Biology
• Cancer Therapeutics

Background:

• Proliferating cell nuclear antigen (PCNA) is a crucial scaffold protein with established roles in DNA replication, repair, and damage tolerance.
• Emerging evidence highlights non-canonical, cytosolic functions of PCNA in immune evasion, apoptosis, metabolism, and signaling.

Purpose of the Study:

• To explore the multifaceted roles of PCNA beyond its canonical DNA-associated functions.
• To investigate the potential of targeting stress-related PCNA functions for novel cancer therapies.

Main Methods:

• Literature review and synthesis of existing research on PCNA functions.
• Analysis of PCNA's protein interactions and regulatory mechanisms.
• Discussion of therapeutic strategies targeting PCNA in cancer.

Main Results:

• PCNA's functions extend to cytosolic pathways regulating critical cellular processes.
• PCNA's diverse roles are mediated by extensive protein interactions.
• Targeting PCNA presents a therapeutic opportunity, but selectivity remains a challenge.

Conclusions:

• PCNA's non-canonical roles are integral to cellular processes and cancer progression.
• Exploiting stress-related PCNA functions may enable selective cancer cell killing.
• Developing targeted PCNA therapies requires careful consideration of toxicity to healthy cells.