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Targeting PCNA in Cancer: A Paradigm Shift from Static Inhibition to Dynamic Network Modulation
Shijia Lu1, Yanmin Wang1, Han Zhang1
1School of Life Science and Technology, North Henan Medical University, Xinxiang, China.
Oncology Research
|July 25, 2026
Summary
Targeting Proliferating Cell Nuclear Antigen (PCNA) offers a promising anticancer strategy. Overcoming challenges in selectivity and delivery is key to developing effective PCNA-based therapies for cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Proliferating Cell Nuclear Antigen (PCNA) is crucial for DNA replication and repair.
- PCNA dysregulation contributes to cancer development and treatment resistance.
- Targeting PCNA presents a challenge due to its essential role in normal cells.
Purpose of the Study:
- To systematically review advances in PCNA-targeted cancer therapy.
- To analyze intervention strategies, their potential, and limitations.
- To identify bottlenecks hindering clinical translation and explore novel solutions.
Main Methods:
- Review of small-molecule inhibitors, proteolysis-targeting chimeras, and other PCNA-targeting approaches.
- Analysis of preclinical data on efficacy and safety.
- Examination of emerging technologies like AI and synthetic biology.
Main Results:
- Various PCNA-targeting strategies show preclinical promise but face selectivity and delivery challenges.
- Resistance evolution is a significant hurdle for sustained therapeutic effect.
- Emerging technologies offer potential but are in early developmental stages.
Conclusions:
- Developing selective PCNA-based anticancer therapies requires addressing key translational dilemmas.
- Cross-disciplinary approaches may overcome current limitations.
- Further research is needed to translate preclinical findings into clinical applications.
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