Targeting the master of the replication fork-PCNA

Area of Science:

• Oncology
• Molecular Biology
• Drug Discovery

Background:

• Proliferating Cell Nuclear Antigen (PCNA) is crucial for DNA replication, repair, and cell-cycle control.
• Tumors exhibit hyperproliferation and genomic instability, making them highly reliant on PCNA.
• This dependency presents a therapeutic vulnerability for cancer treatment.

Purpose of the Study:

• To review the mechanistic rationale behind targeting PCNA in cancer therapy.
• To explore various therapeutic modalities aimed at PCNA.
• To summarize the current development landscape of PCNA-targeted interventions.

Main Methods:

• Review of preclinical and clinical studies on PCNA-targeted agents.
• Analysis of strategies including direct PCNA inhibition and disruption of PCNA-partner interactions.
• Evaluation of combination regimens with DNA-damaging agents.

Main Results:

• Several agents, including ATX-101 and AOH1996, are in early clinical trials.
• PCNA-targeted therapies are being investigated as monotherapies and in combination treatments.
• These interventions aim to enhance chemo- and radiosensitivity.

Conclusions:

• Targeting PCNA represents a promising strategy to improve anticancer efficacy.
• PCNA inhibition may lead to enhanced sensitivity to chemotherapy and radiotherapy.
• Future development focuses on optimizing PCNA-targeted interventions to improve patient outcomes while minimizing toxicity.