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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
PubMed

Insights

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.
Keywords:
Proliferating cell nuclear antigenartificial intelligenceclinical translationprecision therapysynthetic lethalitytargeted protein degradationtumor microenvironment

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